APP

Summary

Gene Symbol: APP
Description: amyloid beta precursor protein
Alias: AAA, ABETA, ABPP, AD1, APPI, CTFgamma, CVAP, PN-II, PN2, amyloid beta A4 protein, alzheimer disease amyloid protein, amyloid beta (A4) precursor protein, amyloid precursor protein, beta-amyloid peptide, beta-amyloid peptide(1-40), beta-amyloid peptide(1-42), beta-amyloid precursor protein, cerebral vascular amyloid peptide, peptidase nexin-II, preA4, protease nexin-II, testicular tissue protein Li 2
Species: human

Top Publications

  1. ncbi Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity
    N Kitaguchi
    Life Science Research Laboratories, Asahi Chemical Industry Co Ltd, Shizuoka, Japan
    Nature 331:530-2. 1988
  2. ncbi Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
    Rakez Kayed
    Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697 3900, USA
    Science 300:486-9. 2003
  3. ncbi Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo
    Dominic M Walsh
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nature 416:535-9. 2002
  4. pmc Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory
    Ganesh M Shankar
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nat Med 14:837-42. 2008
  5. pmc Amyloid plaque core protein in Alzheimer disease and Down syndrome
    C L Masters
    Proc Natl Acad Sci U S A 82:4245-9. 1985
  6. pmc Prion protein interacts with BACE1 protein and differentially regulates its activity toward wild type and Swedish mutant amyloid precursor protein
    Heledd H Griffiths
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Biol Chem 286:33489-500. 2011
  7. ncbi A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid
    M Mullan
    Alzheimer s Disease Research Laboratories, Suncoast Gerontology Center, Tampa, Florida
    Nat Genet 1:345-7. 1992
  8. ncbi Self-propagating, molecular-level polymorphism in Alzheimer's beta-amyloid fibrils
    Aneta T Petkova
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health NIH, Bethesda, MD 20892 0520, USA
    Science 307:262-5. 2005
  9. ncbi Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE
    R Vassar
    Amgen, Inc, One Amgen Center Drive, M S 29 2 B, Thousand Oaks, CA 91320 1799, USA
    Science 286:735-41. 1999
  10. pmc GxxxG motifs within the amyloid precursor protein transmembrane sequence are critical for the etiology of Abeta42
    Lisa Marie Munter
    Institut fur Chemie und Biochemie, Freie Universitat Berlin, Berlin, Germany
    EMBO J 26:1702-12. 2007

Research Grants

  1. David B Teplow; Fiscal Year: 2014
  2. Synaptic damage in models of beta-amyloid associated pathology
    Edward H Koo; Fiscal Year: 2011
  3. Yong Shen; Fiscal Year: 2014
  4. Synaptic dysregulation in a mouse model of Alzheimer's disease
    Daniel A Nicholson; Fiscal Year: 2011
  5. Kumar Sambamurti; Fiscal Year: 2014
  6. Suman Jayadev; Fiscal Year: 2015
  7. Rick B Meeker; Fiscal Year: 2016
  8. Suman Jayadev; Fiscal Year: 2016
  9. Jessica O Wilson; Fiscal Year: 2014
  10. Age-related Response of Hippocampal Neurons to Stress
    Gregory Brewer; Fiscal Year: 2009

Patents

  1. Precursor protein of APC polypeptide, DNA coding therefor and diagnostic use of the DNA and protein

Detail Information

Publications412 found, 100 shown here

  1. ncbi Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity
    N Kitaguchi
    Life Science Research Laboratories, Asahi Chemical Industry Co Ltd, Shizuoka, Japan
    Nature 331:530-2. 1988
    ..AP) as senile plaque core and vascular amyloid, and a complementary DNA encoding a precursor of this protein (APP) has been cloned from human brain...
  2. ncbi Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
    Rakez Kayed
    Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697 3900, USA
    Science 300:486-9. 2003
    Soluble oligomers are common to most amyloids and may represent the primary toxic species of amyloids, like the Abeta peptide in Alzheimer's disease (AD)...
  3. ncbi Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo
    Dominic M Walsh
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nature 416:535-9. 2002
    Although extensive data support a central pathogenic role for amyloid beta protein (Abeta) in Alzheimer's disease, the amyloid hypothesis remains controversial, in part because a specific neurotoxic species of Abeta and the nature of its ..
  4. pmc Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory
    Ganesh M Shankar
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nat Med 14:837-42. 2008
    ..We extracted soluble amyloid-beta protein (Abeta) oligomers directly from the cerebral cortex of subjects with Alzheimer's disease...
  5. pmc Amyloid plaque core protein in Alzheimer disease and Down syndrome
    C L Masters
    Proc Natl Acad Sci U S A 82:4245-9. 1985
    ....
  6. pmc Prion protein interacts with BACE1 protein and differentially regulates its activity toward wild type and Swedish mutant amyloid precursor protein
    Heledd H Griffiths
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Biol Chem 286:33489-500. 2011
    In Alzheimer disease amyloid-β (Aβ) peptides derived from the amyloid precursor protein (APP) accumulate in the brain. Cleavage of APP by the β-secretase BACE1 is the rate-limiting step in the production of Aβ...
  7. ncbi A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid
    M Mullan
    Alzheimer s Disease Research Laboratories, Suncoast Gerontology Center, Tampa, Florida
    Nat Genet 1:345-7. 1992
    Mutations at codon 717 in exon 17 of the beta-amyloid precursor protein (APP) gene have previously been shown to segregate with early onset Alzheimer's disease in some families...
  8. ncbi Self-propagating, molecular-level polymorphism in Alzheimer's beta-amyloid fibrils
    Aneta T Petkova
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health NIH, Bethesda, MD 20892 0520, USA
    Science 307:262-5. 2005
    ..magnetic resonance measurements on fibrils formed by the 40-residue beta-amyloid peptide of Alzheimer's disease (Abeta(1-40)), we show that different fibril morphologies have different underlying molecular structures, that the ..
  9. ncbi Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE
    R Vassar
    Amgen, Inc, One Amgen Center Drive, M S 29 2 B, Thousand Oaks, CA 91320 1799, USA
    Science 286:735-41. 1999
    ..Abeta generation depends on proteolytic cleavage of the amyloid precursor protein (APP) by two unknown proteases: beta-secretase and gamma-secretase...
  10. pmc GxxxG motifs within the amyloid precursor protein transmembrane sequence are critical for the etiology of Abeta42
    Lisa Marie Munter
    Institut fur Chemie und Biochemie, Freie Universitat Berlin, Berlin, Germany
    EMBO J 26:1702-12. 2007
    Processing of the amyloid precursor protein (APP) by beta- and gamma-secretases leads to the generation of amyloid-beta (Abeta) peptides with varying lengths...
  11. pmc Cellular prion protein regulates beta-secretase cleavage of the Alzheimer's amyloid precursor protein
    Edward T Parkin
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, United Kingdom
    Proc Natl Acad Sci U S A 104:11062-7. 2007
    Proteolytic processing of the amyloid precursor protein (APP) by beta-secretase, beta-site APP cleaving enzyme (BACE1), is the initial step in the production of the amyloid beta (Abeta) peptide, which is involved in the pathogenesis of ..
  12. pmc Interaction between human prion protein and amyloid-beta (Abeta) oligomers: role OF N-terminal residues
    Shugui Chen
    Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 285:26377-83. 2010
    ..the role of PrP codon 129 polymorphism as a risk factor in AD is due to factors unrelated to the interaction with Abeta oligomers...
  13. ncbi Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation
    F G Gervais
    Department of Pharmacology, Biochemistry, and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Merck Research Laboratories, Kirkland, Quebec, Canada
    Cell 97:395-406. 1999
    The amyloid-beta precursor protein (APP) is directly and efficiently cleaved by caspases during apoptosis, resulting in elevated amyloid-beta (A beta) peptide formation...
  14. pmc Secreted APP regulates the function of full-length APP in neurite outgrowth through interaction with integrin beta1
    Tracy L Young-Pearse
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Neural Dev 3:15. 2008
    Beta-amyloid precursor protein (APP) has been reported to play a role in the outgrowth of neurites from cultured neurons...
  15. ncbi Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease
    A Goate
    Department of Biochemistry, St Mary s Hospital Medical School, London, UK
    Nature 349:704-6. 1991
    A locus segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21, close to the amyloid precursor protein (APP) gene...
  16. pmc The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol
    Paul J Barrett
    Department of Biochemistry, Center for Structural Biology and Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, TN 37232 USA
    Science 336:1168-71. 2012
    C99 is the transmembrane carboxyl-terminal domain of the amyloid precursor protein that is cleaved by γ-secretase to release the amyloid-β polypeptides, which are associated with Alzheimer's disease...
  17. pmc The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein
    J P Borg
    Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor 48109, USA
    Mol Cell Biol 16:6229-41. 1996
    ..of X11 and one of the PI domains of FE65, two neuronal proteins, bind to the cytoplasmic domain of the amyloid precursor protein ((beta)APP). (beta)APP is an integral transmembrane glycoprotein whose cellular function is unknown...
  18. ncbi Identification and characterization of key kinetic intermediates in amyloid beta-protein fibrillogenesis
    M D Kirkitadze
    Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Mol Biol 312:1103-19. 2001
    Amyloid beta-protein (Abeta) assembly into toxic oligomeric and fibrillar structures is a seminal event in Alzheimer's disease, therefore blocking this process could have significant therapeutic benefit...
  19. pmc Amyloidogenic processing but not amyloid precursor protein (APP) intracellular C-terminal domain production requires a precisely oriented APP dimer assembled by transmembrane GXXXG motifs
    Pascal Kienlen-Campard
    Center for Neurosciences, Experimental Pharmacology Unit, Universite Catholique de Louvain, B 1200 Brussels, Belgium
    J Biol Chem 283:7733-44. 2008
    ..Abeta is produced by the sequential cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases...
  20. ncbi A specific amyloid-beta protein assembly in the brain impairs memory
    Sylvain Lesne
    Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
    Nature 440:352-7. 2006
    ..Tg2576 mice are caused by the extracellular accumulation of a 56-kDa soluble amyloid-beta assembly, which we term Abeta*56 (Abeta star 56)...
  21. pmc Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology
    Rebecca Radde
    Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, Otfried Muller Strasse 27, D 72076 Tubingen, Germany
    EMBO Rep 7:940-6. 2006
    ..a novel transgenic mouse model on a C57BL/6J genetic background that coexpresses KM670/671NL mutated amyloid precursor protein and L166P mutated presenilin 1 under the control of a neuron-specific Thy1 promoter element (APPPS1 mice)..
  22. pmc ADP ribosylation factor 6 (ARF6) controls amyloid precursor protein (APP) processing by mediating the endosomal sorting of BACE1
    Ragna Sannerud
    Laboratory of Membrane Trafficking, Center for Human Genetics, Catholic University of Leuven, Leuven, Belgium
    Proc Natl Acad Sci U S A 108:E559-68. 2011
    ..and a hallmark in Alzheimer's disease pathology, are generated through the sequential cleavage of amyloid precursor protein (APP) by β-site APP cleaving enzyme 1 (BACE1) and γ-secretase...
  23. ncbi Dissection of amyloid-beta precursor protein-dependent transcriptional transactivation
    Xinwei Cao
    Center for Basic Neuroscience, Department of Molecular Genetics, and Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9111, USA
    J Biol Chem 279:24601-11. 2004
    Amyloid-beta precursor protein (APP) forms a transcriptionally active complex with the adaptor protein Fe65 and the histone acetyltransferase Tip60, but the mechanism of transcriptional activation that is mediated by APP and Fe65 remains ..
  24. pmc The novel cargo Alcadein induces vesicle association of kinesin-1 motor components and activates axonal transport
    Yoichi Araki
    Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
    EMBO J 26:1475-86. 2007
    ..vesicles were transported with a velocity different from that of amyloid beta-protein precursor (APP)-containing vesicles, which are transported by the same kinesin-1 motor...
  25. pmc Alzheimer's disease-like pathological features in transgenic mice expressing the APP intracellular domain
    Kaushik Ghosal
    Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 106:18367-72. 2009
    ..Yet, many observations are inconsistent with the hypothesis. Abeta peptides are generated when amyloid precursor protein (APP) is cleaved by presenilins, a process that also produces APP intracellular domain (AICD)...
  26. doi Loss of HRD1-mediated protein degradation causes amyloid precursor protein accumulation and amyloid-beta generation
    Masayuki Kaneko
    Department of Pharmacology, Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Chiba 288 0025, Japan
    J Neurosci 30:3924-32. 2010
    ..HRD1 is expressed in brain neurons and acts as an ERAD ubiquitin ligase. Amyloid precursor protein (APP) is processed into amyloid-beta peptides (Abetas) that form plaque deposits in the brains of ..
  27. pmc Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease
    Heng Du
    Department of Surgery, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, New York 10032, USA
    Nat Med 14:1097-105. 2008
    ..Here we show that interaction of CypD with mitochondrial amyloid-beta protein (Abeta) potentiates mitochondrial, neuronal and synaptic stress...
  28. ncbi Molecular dissection of the interaction between amyloid precursor protein and its neuronal trafficking receptor SorLA/LR11
    Olav M Andersen
    Max Delbrueck Center for Molecular Medicine, Berlin, 13125 Berlin, Germany
    Biochemistry 45:2618-28. 2006
    SorLA/LR11 is a sorting receptor that regulates the intracellular transport and processing of the amyloid precursor protein (APP) in neurons...
  29. pmc Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP
    Rita Joao Guerreiro
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
    Neurobiol Aging 31:725-31. 2010
    Mutations in three genes (PSEN1, PSEN2, and APP) have been identified in patients with early-onset (<65 years) Alzheimer's disease (AD)...
  30. doi Lipid matrix plays a role in Abeta fibril kinetics and morphology
    Marc Antoine Sani
    School of Chemistry, Bio21 Institute, University of Melbourne, VIC 3010, Australia
    FEBS Lett 585:749-54. 2011
    ..Circular dichroism and thioflavin T assays confirmed an initially unstructured peptide, and measured its transition to an aggregated beta-sheet conformation...
  31. ncbi Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I
    A Kamal
    Howard Hughes Medical Institute, Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla 92093, USA
    Neuron 28:449-59. 2000
    We analyzed the mechanism of axonal transport of the amyloid precursor protein (APP), which plays a major role in the development of Alzheimer's disease...
  32. ncbi Beta amyloid peptide (Abeta42) is internalized via the G-protein-coupled receptor FPRL1 and forms fibrillar aggregates in macrophages
    H Yazawa
    Laboratory of Molecular Immunoregulation, SAIC Frederick, Center for Cancer Research, National Cancer Institute at Frederick, Maryland 21702, USA
    FASEB J 15:2454-62. 2001
    ..These results suggest that besides mediating the proinflammatory activity of Abeta42, FPRL1 is also involved in the internalization of Abeta42, which culminates in the formation of fibrils only in macrophages...
  33. pmc S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury
    Dong Hyung Cho
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 324:102-5. 2009
    ..Preventing nitrosylation of Drp1 by cysteine mutation abrogated these neurotoxic events. SNO-Drp1 is increased in brains of human Alzheimer's disease patients and may thus contribute to the pathogenesis of neurodegeneration...
  34. doi Phosphorylation of APP-CTF-AICD domains and interaction with adaptor proteins: signal transduction and/or transcriptional role--relevance for Alzheimer pathology
    Gennaro Schettini
    Department of Oncology, Biology and Genetics, University of Genova, Genova, Italy
    J Neurochem 115:1299-308. 2010
    In recent decades, the study of the amyloid precursor protein (APP) and of its proteolytic products carboxy terminal fragment (CTF), APP intracellular C-terminal domain (AICD) and amyloid beta has been mostly focussed on the role of APP ..
  35. doi Intraneuronal amyloid β oligomers cause cell death via endoplasmic reticulum stress, endosomal/lysosomal leakage, and mitochondrial dysfunction in vivo
    Tomohiro Umeda
    Department of Neuroscience, Osaka City University Graduate School of Medicine, Osaka, Japan
    J Neurosci Res 89:1031-42. 2011
    ..Previously, we showed that the E693Δ mutation (referred to as the "Osaka" mutation) of amyloid precursor protein (APP) caused intracellular accumulation of Aβ oligomers and apoptosis in transfected COS-7 cells...
  36. pmc GGA1-mediated endocytic traffic of LR11/SorLA alters APP intracellular distribution and amyloid-β production
    Jeremy H Herskowitz
    Center for Neurodegenerative Disease, Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Mol Biol Cell 23:2645-57. 2012
    Proteolytic processing of the amyloid-β precursor protein (APP) and generation of amyloid-β peptide (Aβ) are key events in Alzheimer's disease (AD) pathogenesis...
  37. ncbi Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease
    R E Tanzi
    Neurogenetics Laboratory, Massachusetts General Hospital, Boston 02115
    Nature 331:528-30. 1988
    ..The amyloid protein precursor (APP) gene is expressed in brain and in several peripheral tissues, but the specific biochemical events leading to ..
  38. ncbi Cleavage of amyloid-beta precursor protein and amyloid-beta precursor-like protein by BACE 1
    Qiming Li
    Center for Basic Neuroscience, Department of Molecular Genetics and Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9111, USA
    J Biol Chem 279:10542-50. 2004
    ..fragment (called APP(S)), peptides of 40-43 residues derived from extracellular and transmembrane sequences (Abeta), and a short intracellular fragment (APP intracellular domain) that may function as a transcriptional activator ..
  39. doi A metabolomic study of the CRND8 transgenic mouse model of Alzheimer's disease
    Reza M Salek
    Department of Biochemistry, The Hopkins Building, Tennis Court Road, University of Cambridge, Cambridge CB21QW, UK
    Neurochem Int 56:937-47. 2010
    ..In this study the transgenic mouse TgCRND8, which encodes a mutant form of the amyloid precursor protein 695 with both the Swedish and Indiana mutations and develops extracellular amyloid beta-peptide deposits ..
  40. pmc Altered levels and distribution of amyloid precursor protein and its processing enzymes in Niemann-Pick type C1-deficient mouse brains
    A Kodam
    Department of Psychiatry, Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada
    Glia 58:1267-81. 2010
    ..Abeta)-related peptides in vulnerable brain regions, but very little is known about the expression of amyloid precursor protein (APP) or APP secretases in NPC disease...
  41. ncbi Role of phosphorylation of Alzheimer's amyloid precursor protein during neuronal differentiation
    K Ando
    Laboratory of Neurobiophysics, School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo, 113 0033 Japan
    J Neurosci 19:4421-7. 1999
    Alzheimer's amyloid precursor protein (APP), the precursor of beta-amyloid (Abeta), is an integral membrane protein with a receptor-like structure...
  42. ncbi The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
    J Kang
    Nature 325:733-6. 1987
    ..This sequence, together with the localization of its gene on chromosome 21, suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor...
  43. ncbi The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner
    W T Kimberly
    Department of Neurology, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Biol Chem 276:40288-92. 2001
    The beta-amyloid precursor protein (APP) is a ubiquitous receptor-like molecule without a known function...
  44. doi A new amyloid beta variant favoring oligomerization in Alzheimer's-type dementia
    Takami Tomiyama
    Department of Neuroscience, Osaka City University Graduate School of Medicine, Osaka, Japan
    Ann Neurol 63:377-87. 2008
    ..However, there is no direct evidence in humans that this mechanism can cause AD. Here, we report a novel amyloid precursor protein (APP) mutation that may provide evidence to address this question.
  45. pmc Proteolytic processing of Alzheimer's β-amyloid precursor protein
    Han Zhang
    Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, College of Medicine, Xiamen University, Xiamen, Fujian, China
    J Neurochem 120:9-21. 2012
    b>Amyloid precursor protein (APP) is a critical factor in the pathogenesis of Alzheimer's disease (AD). APP undergoes post-translational proteolysis/processing to generate the hydrophobic β-amyloid (Aβ) peptides...
  46. ncbi Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy
    T J Grabowski
    Department of Neurology and Radiology, College of Medicine, University of Iowa, Iowa City, USA
    Ann Neurol 49:697-705. 2001
    Several mutations in the amyloid precursor protein (APP) gene have been found to associate with pathologic deposition of the beta-amyloid peptide (Abeta) in neuritic plaques or in the walls of cerebral vessels...
  47. ncbi Calcium dysregulation and membrane disruption as a ubiquitous neurotoxic mechanism of soluble amyloid oligomers
    Angelo Demuro
    Department of Neurobiology and Behavior and Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA
    J Biol Chem 280:17294-300. 2005
    ..disruptions in amyloid-induced cytotoxicity, we made homogeneous preparations of disease-related amyloids (Abeta, prion, islet amyloid polypeptide, polyglutamine, and lysozyme) in various aggregation states and tested their ..
  48. ncbi Secretion of the Notch-1 Abeta-like peptide during Notch signaling
    Masayasu Okochi
    Department of Post Genomics and Diseases, Division of Psychiatry and Behavioral Proteomics, Osaka University Graduate School of Medicine, Osaka 565 0871, Japan
    J Biol Chem 281:7890-8. 2006
    ..require an additional cleavage near the middle of the transmembrane domain, extracellular small peptides (Notch-1 Abeta-like peptide (Nbeta)) should be produced...
  49. pmc Structure of alpha-helical membrane-bound human islet amyloid polypeptide and its implications for membrane-mediated misfolding
    Melania Apostolidou
    Department of Biochemistry and Molecular Biology, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    J Biol Chem 283:17205-10. 2008
    ..Based upon these considerations, a structural model for membrane-mediated aggregation is discussed...
  50. doi β-Barrel topology of Alzheimer's β-amyloid ion channels
    Hyunbum Jang
    Center for Cancer Research Nanobiology Program, SAIC Frederick, Inc, National Cancer Institute Frederick, Frederick, MD 21702, USA
    J Mol Biol 404:917-34. 2010
    ..The subunits appear mobile, allowing unregulated, hence toxic, ion flux...
  51. ncbi Variations in the APP gene promoter region and risk of Alzheimer disease
    L Guyant-Marechal
    INSERM U614, Faculty of Medicine, IFRMP, 76000 Rouen, France
    Neurology 68:684-7. 2007
    ..By contrast, analysis of three recently described rare mutations influencing APP transcription did not confirm their association with AD risk.
  52. ncbi Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease
    D Goldgaber
    Science 235:877-80. 1987
    ..The 3.5-kilobase messenger RNA was detected in mammalian brains and human thymus. The gene is highly conserved in evolution and has been mapped to human chromosome 21...
  53. ncbi Caspase-6 role in apoptosis of human neurons, amyloidogenesis, and Alzheimer's disease
    A Leblanc
    Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3T 1E2, Canada
    J Biol Chem 274:23426-36. 1999
    ..Abeta is a consequence of neuronal apoptosis, suggesting that apoptosis activates proteases involved in amyloid precursor protein (APP) processing...
  54. pmc Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer's disease cases
    Oliver Wirths
    Division of Molecular Psychiatry, Department of Psychiatry, University of Goettingen, Gottingen, Germany
    J Neural Transm (Vienna) 117:85-96. 2010
    The presence of Abeta(pE3) (N-terminal truncated Abeta starting with pyroglutamate) in Alzheimer's disease (AD) has received considerable attention since the discovery that this peptide represents a dominant fraction of Abeta peptides in ..
  55. pmc Valproic acid inhibits Abeta production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models
    Hong Qing
    Department of Psychiatry, Townsend Family Laboratories, Brain Research Center, University of British Columbia, Vancouver, BC, Canada
    J Exp Med 205:2781-9. 2008
    ..Amyloid beta-protein (Abeta), the central component of neuritic plaques, is derived from beta-amyloid precursor protein (APP) after beta- and gamma-secretase cleavage...
  56. ncbi A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease
    J Murrell
    Indiana University School of Medicine, Department of Medicine
    Science 254:97-9. 1991
    ..disease revealed a single amino acid substitution (Phe for Val) in the transmembrane domain of the amyloid precursor protein. This mutation correlates with the presence of Alzheimer's disease in all patients in this study, and ..
  57. ncbi LDL receptor-related protein, a multifunctional ApoE receptor, binds secreted beta-amyloid precursor protein and mediates its degradation
    M Z Kounnas
    Department of Biochemistry, Holland Laboratories, American Red Cross, Rockville, Maryland 20855, USA
    Cell 82:331-40. 1995
    The secreted form of beta-amyloid precursor protein (APP) containing the Kunitz proteinase inhibitor (KPI) domain, also called protease nexin II, is internalized and degraded by cells...
  58. pmc Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum
    D Campion
    INSERM EPI 9906, Faculte de Medecine, 76183 Rouen, France
    Am J Hum Genet 65:664-70. 1999
    ..2 and 5.3, respectively. We then performed a mutational analysis of the genes for amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) in 34 families with ADEOAD ascertained in France...
  59. ncbi Amyloidogenic processing of beta-amyloid precursor protein in intracellular compartments
    Kulandaivelu S Vetrivel
    Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, IL 60637, USA
    Neurology 66:S69-73. 2006
    Trafficking and proteolytic processing of amyloid precursor protein (APP) have been the focus of numerous investigations in the past two decades, since the identification of Abeta as the principal component of brain senile plaques and ..
  60. doi Antiparallel beta-sheet: a signature structure of the oligomeric amyloid beta-peptide
    Emilie Cerf
    Center for Structural Biology and Bioinformatics, Laboratory for Structure and Function of Biological Membranes, Faculte des Sciences, Universite Libre de Bruxelles, CP 206 2, Blvd du Triomphe, B 1050 Brussels, Belgium
    Biochem J 421:415-23. 2009
    AD (Alzheimer's disease) is linked to Abeta (amyloid beta-peptide) misfolding. Studies demonstrate that the level of soluble Abeta oligomeric forms correlates better with the progression of the disease than the level of fibrillar forms...
  61. doi Overexpression of wild-type human APP in mice causes cognitive deficits and pathological features unrelated to Abeta levels
    Ana María Simón
    Division of Neurosciences, CIMA, University of Navarra, Av Pio XII 55, 31008 Pamplona, Spain
    Neurobiol Dis 33:369-78. 2009
    Transgenic mice expressing mutant human amyloid precursor protein (APP) develop an age-dependent amyloid pathology and memory deficits, but no overt neuronal loss...
  62. pmc The amyloid-beta precursor protein: integrating structure with biological function
    Constanze Reinhard
    Laboratory for Neuronal Cell Biology and Gene Transfer, Department of Human Genetics, Center for Human Genetics, KU Leuven and VIB, Leuven, Belgium
    EMBO J 24:3996-4006. 2005
    Proteolytic processing of the amyloid-beta precursor protein (APP) generates the Abeta amyloid peptide of Alzheimer's disease. The biological function of APP itself remains, however, unclear...
  63. doi Abnormal cleavage of APP impairs its functions in cell adhesion and migration
    Baiyang Sheng
    State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China
    Neurosci Lett 450:327-31. 2009
    b>Amyloid precursor protein (APP) is expressed ubiquitously but its wrong cleavage only occurs in central nervous system...
  64. pmc Age-dependent accumulation of soluble amyloid beta (Abeta) oligomers reverses the neuroprotective effect of soluble amyloid precursor protein-alpha (sAPP(alpha)) by modulating phosphatidylinositol 3-kinase (PI3K)/Akt-GSK-3beta pathway in Alzheimer mouse m
    Sebastian Jimenez
    Departamento Bioquimica y Biologia Molecular, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain
    J Biol Chem 286:18414-25. 2011
    ..Using N2a and primary neuronal cell cultures, we demonstrated that soluble amyloid precursor protein-α (sAPPα), the predominant APP-derived fragment in young PS1×APP mice, acting through IGF-1 and/or ..
  65. pmc Dynamics of amyloid β fibrils revealed by solid-state NMR
    Holger A Scheidt
    Institute of Medical Physics and Biophysics, University of Leipzig, D 04107 Leipzig, Germany
    J Biol Chem 287:2017-21. 2012
    ..4 and 0.8. Interestingly, the order parameters increase again for the first two residues, Asp(1) and Ala(2), suggesting that the N terminus could carry some structural importance...
  66. doi Characterization of mitochondrial dysfunction in the 7PA2 cell model of Alzheimer's disease
    Nina Krako
    Scuola Normale Superiore, Pisa, Italy European Brain Research Institute Rita Levi Montalcini, Rome, Italy
    J Alzheimers Dis 37:747-58. 2013
    ..All functional parameters point to a severe bioenergetic impairment of the AD cells, with the extent of mitochondrial dysfunction being correlated to the accumulation of Aβ peptides and oligomers. ..
  67. ncbi Identification and differential expression of a novel alternative splice isoform of the beta A4 amyloid precursor protein (APP) mRNA in leukocytes and brain microglial cells
    G Konig
    Center for Molecular Biology ZMBH, INF 282, University of Heidelberg, Germany
    J Biol Chem 267:10804-9. 1992
    The gene for the beta A4-amyloid precursor protein (APP) consists of 19 exons which code for a typical N- and O-glycosylated transmembrane protein with four extracellular domains followed by the transmembrane domain and a short ..
  68. ncbi Nonfibrillar diffuse amyloid deposition due to a gamma(42)-secretase site mutation points to an essential role for N-truncated A beta(42) in Alzheimer's disease
    S Kumar-Singh
    Laboratory of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Born Bunge Foundation, University of Antwerp, Universiteitsplein 1, B 2610, Antwerpen, Belgium
    Hum Mol Genet 9:2589-98. 2000
    Amyloidogenic processing of the amyloid precursor protein (APP) with deposition in brain of the 42 amino acid long amyloid beta-peptide (A beta(42)) is considered central to Alzheimer's disease (AD) pathology...
  69. ncbi Amyloid beta protein precursor is involved in the growth of human colon carcinoma cell in vitro and in vivo
    J Y Meng
    Second Department of Pathology, Miyazaki Medical College, Miyazaki, Japan
    Int J Cancer 92:31-9. 2001
    Amyloid beta protein precursor (APP) is a membrane-bound protein ubiquitously expressed in a variety of types of cells. However, its biological functions remain largely uncertain, particularly in non-neural cells and tumors...
  70. ncbi The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation
    C Nilsberth
    Karolinska Institutet, Department of Neurotec, Geriatric Medicine, Novum KFC, S 141 86 Huddinge, Sweden
    Nat Neurosci 4:887-93. 2001
    ..Here we present studies of a pathogenic amyloid precursor protein (APP) mutation, located within the Abeta sequence at codon 693 (E693G), that causes AD in a Swedish ..
  71. pmc Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes
    Jiyeon Lee
    Department of Pediatrics and Cell Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 283:11501-8. 2008
    Accumulation of extracellular amyloid beta peptide (Abeta), generated from amyloid precursor protein (APP) processing by beta- and gamma-secretases, is toxic to neurons and is central to the pathogenesis of Alzheimer disease...
  72. pmc Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins
    Xinglong Wang
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 105:19318-23. 2008
    ..In this study, we investigated the effect of amyloid precursor protein (APP) and amyloid beta on mitochondrial dynamics in neurons...
  73. pmc Alzheimer's-related endosome dysfunction in Down syndrome is Abeta-independent but requires APP and is reversed by BACE-1 inhibition
    Ying Jiang
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY 10962, USA
    Proc Natl Acad Sci U S A 107:1630-5. 2010
    An additional copy of the beta-amyloid precursor protein (APP) gene causes early-onset Alzheimer's disease (AD) in trisomy 21 (DS)...
  74. pmc Sorting of the Alzheimer's disease amyloid precursor protein mediated by the AP-4 complex
    Patricia V Burgos
    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Dev Cell 18:425-36. 2010
    ..we report the interaction of an YKFFE sequence from the cytosolic tail of the Alzheimer's disease amyloid precursor protein (APP) with the mu4 subunit of AP-4...
  75. pmc Decreased clearance of CNS beta-amyloid in Alzheimer's disease
    Kwasi G Mawuenyega
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 330:1774. 2010
    ..On average, there were no differences in Aβ40 or Aβ42 production rates. Thus, the common late-onset form of Alzheimer's disease is characterized by an overall impairment in Aβ clearance...
  76. pmc Recent progress in understanding Alzheimer's β-amyloid structures
    Marcus Fändrich
    Max Planck Research Unit for Enzymology of Protein Folding and Martin Luther University Halle Wittenberg, Halle Saale, Germany
    Trends Biochem Sci 36:338-45. 2011
    ..These data have significantly enhanced our understanding of the mechanism of Aβ aggregation and have illuminated the possible relevance of specific conformers for neurodegenerative pathologies...
  77. pmc Binding of the molecular chaperone αB-crystallin to Aβ amyloid fibrils inhibits fibril elongation
    Sarah L Shammas
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
    Biophys J 101:1681-9. 2011
    ....
  78. doi FBL2 regulates amyloid precursor protein (APP) metabolism by promoting ubiquitination-dependent APP degradation and inhibition of APP endocytosis
    Tomomichi Watanabe
    CNS Drug Discovery Unit, Oncology Drug Discovery Unit, Evotec Neurosciences, 8008 Zurich, Switzerland
    J Neurosci 32:3352-65. 2012
    ..F-box and leucine rich repeat protein2 (FBL2), a component of the E3 ubiquitin ligase complex, regulates amyloid precursor protein (APP) metabolism through APP ubiquitination...
  79. pmc Adaptor protein 2-mediated endocytosis of the β-secretase BACE1 is dispensable for amyloid precursor protein processing
    Yogikala Prabhu
    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biol Cell 23:2339-51. 2012
    The β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a transmembrane aspartyl protease that catalyzes the proteolytic processing of APP and other plasma membrane protein precursors...
  80. pmc Amyloid-β induced signaling by cellular prion protein and Fyn kinase in Alzheimer disease
    Ji Won Um
    Cellular Neuroscience, Neurodegeneration and Repair Program, Department of Neurology, Yale University School of Medicine, New Haven, CT, USA
    Prion 7:37-41. 2013
    ..These studies suggest that PrP(C) has a central role in AD pathogenesis and may provide a target for therapeutic intervention in AD...
  81. pmc The β-secretase-derived C-terminal fragment of βAPP, C99, but not Aβ, is a key contributor to early intraneuronal lesions in triple-transgenic mouse hippocampus
    Inger Lauritzen
    Universite de Nice Sophia Antipolis, Institut de Pharmacologie Moleculaire et Cellulaire, CNRS UMR 7275, Team Fondation pour la Recherche Médicale and Laboratoire d Excellence Distalz, 06560 Sophia Antipolis, France
    J Neurosci 32:16243-55a. 2012
    Triple-transgenic mice (3xTgAD) overexpressing Swedish-mutated β-amyloid precursor protein (βAPP(swe)), P310L-Tau (Tau(P301L)), and physiological levels of M146V-presenilin-1 (PS1(M146V)) display extracellular amyloid-β peptides (Aβ) ..
  82. doi Evaluation of plasma Abeta(40) and Abeta(42) as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairment
    Oskar Hansson
    Clinical Memory Research Unit, Department of Clinical Sciences Malmo, Lund University, Sweden
    Neurobiol Aging 31:357-67. 2010
    Numerous studies have shown a marked decrease of beta-amyloid(42) (Abeta(42)) in the cerebrospinal fluid (CSF) of patients with incipient Alzheimer's disease (AD)...
  83. ncbi The intracellular cytoplasmic domain of the Alzheimer's disease amyloid precursor protein interacts with phosphotyrosine-binding domain proteins in the yeast two-hybrid system
    D M McLoughlin
    Department of Neurology, The Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, UK
    FEBS Lett 397:197-200. 1996
    We have used the yeast two-hybrid system to screen for proteins that interact with the carboxy-terminal domain of APP. Six different clones were isolated and sequence analyses revealed that they encoded domains of a previously described ..
  84. ncbi Copper depletion down-regulates expression of the Alzheimer's disease amyloid-beta precursor protein gene
    Shayne A Bellingham
    Department of Genetics, The University of Melbourne, Parkville, Victoria 3010, Australia
    J Biol Chem 279:20378-86. 2004
    ..by the accumulation of amyloid-beta peptide, which is cleaved from the amyloid-beta precursor protein (APP)...
  85. ncbi Solution conformation and heparin-induced dimerization of the full-length extracellular domain of the human amyloid precursor protein
    Matthias Gralle
    Instituto de Bioquimica Medica, Programa de Bioquimica e Biofisica Celular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21944 590, Brazil
    J Mol Biol 357:493-508. 2006
    Proteolytic cleavage of the amyloid precursor protein (APP) by beta and gamma-secretases gives rise to the beta-amyloid peptide, considered to be a causal factor in Alzheimer's disease...
  86. ncbi The Arctic Alzheimer mutation favors intracellular amyloid-beta production by making amyloid precursor protein less available to alpha-secretase
    Charlotte Sahlin
    Department of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
    J Neurochem 101:854-62. 2007
    Mutations within the amyloid-beta (Abeta) domain of the amyloid precursor protein (APP) typically generate hemorrhagic strokes and vascular amyloid angiopathy. In contrast, the Arctic mutation (APP E693G) results in Alzheimer's disease...
  87. doi Subcellular localization and dimerization of APLP1 are strikingly different from APP and APLP2
    Daniela Kaden
    Institut fur Chemie und Biochemie, Freie Universitat Berlin, Berlin, Germany
    J Cell Sci 122:368-77. 2009
    The molecular association between APP and its mammalian homologs has hardly been explored...
  88. doi Spatial learning and memory impairment and increased locomotion in a transgenic amyloid precursor protein mouse model of Alzheimer's disease
    J M Walker
    Department of Psychological Sciences, 210 McAlester Hall, University of Missouri, Columbia, MO 65211, USA
    Behav Brain Res 222:169-75. 2011
    ..of spatial learning and a behavioral assessment of irritability and locomotion in TgCRND8 mice, an amyloid precursor protein transgenic model of Alzheimer's disease...
  89. pmc Axonal transport of APP and the spatial regulation of APP cleavage and function in neuronal cells
    Silke Brunholz
    Department of Human Biology and Human Genetics, Technical University of Kaiserslautern, Kaiserslautern, Germany
    Exp Brain Res 217:353-64. 2012
    Over two decades have passed since the original discovery of amyloid precursor protein (APP)...
  90. doi Mutant human APP exacerbates pathology in a mouse model of NPC and its reversal by a β-cyclodextrin
    Mahua Maulik
    Department of Medicine Neurology, Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB, Canada
    Hum Mol Genet 21:4857-75. 2012
    ..cholesterol level, which acts as a risk factor for AD, can increase Aβ production by regulating amyloid precursor protein (APP) metabolism, it is possible that APP overexpression can influence cholesterol-regulated NPC ..
  91. ncbi A second cytotoxic proteolytic peptide derived from amyloid beta-protein precursor
    D C Lu
    Program on Aging, The Burnham Institute, La Jolla, California 92037, USA
    Nat Med 6:397-404. 2000
    ..These findings indicate the possibility that caspase cleavage of amyloid beta-protein precursor with the generation of C31 may be involved in the neuronal death associated with Alzheimer disease...
  92. ncbi The Alzheimer's peptide a beta adopts a collapsed coil structure in water
    S Zhang
    Department of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts, 02215, USA
    J Struct Biol 130:130-41. 2000
    The self-assembly of the soluble peptide Abeta into Alzheimer's disease amyloid is believed to involve a conformational change. Hence the solution conformation of Abeta is of significant interest...
  93. ncbi Presenilin-1 regulates intracellular trafficking and cell surface delivery of beta-amyloid precursor protein
    Dongming Cai
    Fisher Center for Research on Alzheimer s Disease and Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, USA
    J Biol Chem 278:3446-54. 2003
    Presenilins (PS1/PS2) play a critical role in proteolysis of beta-amyloid precursor protein (beta APP) to generate beta-amyloid, a peptide important in the pathogenesis of Alzheimer's disease...
  94. pmc Co-localization of amyloid beta and tau pathology in Alzheimer's disease synaptosomes
    Jeffrey A Fein
    School of Nursing, University of California at Los Angeles School of Medicine, Sepulveda Veterans Administration Medical Center, Los Angeles, California 90095 6919, USA
    Am J Pathol 172:1683-92. 2008
    The amyloid cascade hypothesis proposes that amyloid beta (Abeta) pathology precedes and induces tau pathology, but the neuropathological connection between these two lesions has not been demonstrated...
  95. pmc Down-regulation of the ATP-binding cassette transporter 2 (Abca2) reduces amyloid-β production by altering Nicastrin maturation and intracellular localization
    Vasiliki Michaki
    Center for Human Genetics and Leuven Institute for Neurodegenerative Diseases, KU Leuven, 3000 Leuven, Belgium
    J Biol Chem 287:1100-11. 2012
    ..Reduced Abca2 levels in mammalian cells in vitro, in Drosophila melanogaster and in mice resulted in altered γ-secretase processing of APP, and thus Aβ generation, without affecting Notch cleavage.
  96. ncbi The amyloid precursor protein of Alzheimer's disease in the reduction of copper(II) to copper(I)
    G Multhaup
    ZMBH Center for Molecular Biology Heidelberg, University of Heidelberg, Germany
    Science 271:1406-9. 1996
    The transition metal ion copper(II) has a critical role in chronic neurologic diseases. The amyloid precursor protein (APP) of Alzheimer's disease or a synthetic peptide representing its copper-binding site reduced bound copper(II) to ..
  97. ncbi X11alpha modulates secretory and endocytic trafficking and metabolism of amyloid precursor protein: mutational analysis of the YENPTY sequence
    G D King
    Neuroscience Program, University of Michigan, Ann Arbor, MI 48109, USA
    Neuroscience 120:143-54. 2003
    The neuronal adaptor X11alpha interacts with the conserved -GYENPTY- sequence in the C-terminus of amyloid precursor protein (APP) or its Swedish mutation (APPswe) to inhibit Abeta40 and Abeta42 secretion...
  98. pmc APP heterozygosity averts memory deficit in knockin mice expressing the Danish dementia BRI2 mutant
    Robert Tamayev
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
    EMBO J 30:2501-9. 2011
    ..BRI2 is a physiological interactor of Aβ-precursor protein (APP), a gene associated with Alzheimer disease, which inhibits processing of APP...
  99. ncbi An Iranian family with Alzheimer's disease caused by a novel APP mutation (Thr714Ala)
    P Pasalar
    Department of Biochemistry, Tehran University of Medical Sciences, Iran
    Neurology 58:1574-5. 2002
  100. ncbi Mutations that reduce aggregation of the Alzheimer's Abeta42 peptide: an unbiased search for the sequence determinants of Abeta amyloidogenesis
    Christine Wurth
    Department of Chemistry, Princeton University, NJ 08544, USA
    J Mol Biol 319:1279-90. 2002
    ..Although the amino acid residue sequence of Abeta42 is known, the molecular determinants of Abeta amyloidogenesis have not been elucidated...
  101. ncbi ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease
    Joyce W Lustbader
    Center for Reproductive Sciences and Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA
    Science 304:448-52. 2004
    Mitochondrial dysfunction is a hallmark of beta-amyloid (Abeta)-induced neuronal toxicity in Alzheimer's disease (AD)...

Research Grants77

  1. David B Teplow; Fiscal Year: 2014
    ..The project also will be of relevance to Parkinsons, Huntingtons, amyotrophic lateral sclerosis, familial amyloid polyneuropathy, the prionoses, and other neurodegenerative diseases of aging. ..
  2. Synaptic damage in models of beta-amyloid associated pathology
    Edward H Koo; Fiscal Year: 2011
    ..This will be tested by selectively expressing amyloid precursor protein (APP) in CA1 or CAS neurons, respectively, and assessing the function of the synapses between these two ..
  3. Yong Shen; Fiscal Year: 2014
    ..To examine the roles of TNFRII in APP processing, we cross-bred AD transgenic APP23 mice, which express mutant APP and form many A[unreadable] plaques, ..
  4. Synaptic dysregulation in a mouse model of Alzheimer's disease
    Daniel A Nicholson; Fiscal Year: 2011
    ..abstract_text> ..
  5. Kumar Sambamurti; Fiscal Year: 2014
    ..Transgenic mice expressing Amyloid beta protein (A[unreadable]) precursor (APP) deposit amyloid but do not present degeneration phenotypes...
  6. Suman Jayadev; Fiscal Year: 2015
    ..Familial Alzheimer disease (fAD) is associated with mutations in the genes encoding amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2)...
  7. Rick B Meeker; Fiscal Year: 2016
    ..in combination with natural neurotrophins (NGF, proNGF), pathogenic molecules associated with aging (Abeta oligomers) and LM11A-31 to define both deleterious and neuroprotective interactions...
  8. Suman Jayadev; Fiscal Year: 2016
    ..To address this hypothesis we will: A) Generate, characterize and assess APP processing activity in iPSC lines from patient fibroblasts containing PS2 mutations...
  9. Jessica O Wilson; Fiscal Year: 2014
    ..The core of AD pathology is attributed to aberrant processing of Amyloid Precursor Protein (APP), which is encoded on chromosome 21...
  10. Age-related Response of Hippocampal Neurons to Stress
    Gregory Brewer; Fiscal Year: 2009
    ..brought into sharper focus by the question, what is it about aging that causes people with congenital mutations in APP or presenilin to wait decades before invariably developing Alzheimer disease (AD) with cognitive deficits and brain ..
  11. Neurologic Alterations in Alzheimer's Disease
    Bradley T Hyman; Fiscal Year: 2010
    ..Genetic and neuropathological evidence highlight a pathogenic role for Abeta, but the exact mechanism of how Abeta alters neural system function is uncertain...
  12. Peripherally administered gene therapy for Alzheimer's
    Bradley T Hyman; Fiscal Year: 2011
    ..Similarly, we have developed a single-chain anti-Abeta antibody which we will test as an alternative means of diminishing amyloid deposition...
  13. CHRISTOPHER MAGED WILLIAM; Fiscal Year: 2014
    ..Recent in vitro data suggest that the Amyloid Precursor Protein (APP)-derived peptide, Abeta, drives synaptic degeneration through the activation of signaling pathways ..
  14. Isabella A Graef; Fiscal Year: 2014
    ..While genetic studies have clearly confirmed the importance of triplication of the amyloid precursor protein (APP) gene, which is found on chromosome 21 (HSA21), in the pathogenesis of early onset AD in DS ..
  15. Donna M Wilcock; Fiscal Year: 2016
    ..The overall goal of our proposal is to determine the time-course of CBVD pathology when we generate CBVD in APP/PS1 transgenic mice, determine the roles of inflammation and MMPs in the generation of microhemorrhage and ..
  16. Prolyl Isomerase Pin 1 and Neurodegeneration
    Kun Ping Lu; Fiscal Year: 2009
    ..regulates tau function and affects the development of tau-related phenotypes and to examine the role of Pin1 in ABeta-induced neurotoxicity...
  17. Frank M LaFerla; Fiscal Year: 2016
    ..The first novel model we developed is a floxed human APP transgenic mouse that permits ablation of APP expression using Cre recombinase...
  18. Mechanisms of amyloid-beta on wild-type tau pathology and cognitive decline
    MEREDITH ANNE CHABRIER; Fiscal Year: 2012
    ..Additionally, the loxP sites will be utilized to eliminate the APP transgene at three different pathological time points in the double transgenic mice...
  19. Nikolaos K Robakis; Fiscal Year: 2014
    ..technology we employed for PS1 to explore the neuroprotective activities of presenilin 2 (PS2) and the amyloid precursor protein (APP)...
  20. Xiongwei Zhu; Fiscal Year: 2016
    ..To complement the in vivo studies, we will determine the causal involvement of abnormal mitochondrial dynamics in Abeta-induced mitochondrial/neuronal function and further pursue mechanisms underlying Abeta-induced changes in ..
  21. Hui Zheng; Fiscal Year: 2016
    ..tangles (NFT), of which the principal components are A[unreadable] peptides derived from the amyloid precursor protein (APP) and hyper-phosphorylated tau, respectively...
  22. Non-amyloidogenic processing of APP
    Ruben Vidal; Fiscal Year: 2012
    ....
  23. Evaluation of iPS Stem Cells as a Model of Alzheimer Disease
    Clinton T Baldwin; Fiscal Year: 2012
    ..In aim 2, (A) we will test the hypothesis that APP/A2 processing is abnormal in iPS derived neurons and (B) utilize the iPS model system as a discovery tool to ..
  24. Antisense Oligonucleotide Treatment for Alzheimer's Disease
    Susan A Farr; Fiscal Year: 2013
    ..The availability of mice overexpressing human APP provides a translational model for OL-1...
  25. A noninvasive optical imaging of retinal amyloid beta deposits in AD patients
    Maya Koronyo-Hamaoui; Fiscal Year: 2013
    ..At the core of our application is the identification of amyloid-beta protein (Abeta) plaques, characteristic of AD pathology, in postmortem and live human retina of AD patients, and possibly at ..
  26. David B Teplow; Fiscal Year: 2015
    ..Aim 3. To identify and validate AD-relevant genes using a bioinformatics approach that considers A? assembly structure, neuron type, and neuron senescence. ..
  27. RUDOLPH EMILE TANZI; Fiscal Year: 2016
    ..only been resolved at 12 A (under this grant), and small molecules that can selectively inhibit its processing of APP are not yet validated...
  28. Epigenomic impact of diet and toxicant exposure in Alzheimers disease etiology
    Iliya Lefterov; Fiscal Year: 2013
    ..pathological and clinical features of AD including: induced tau hyperphosphorylation, upregulation of amyloid precursor protein (APP);increased cardiovascular disease;enhanced brain inflammatory reactions, hyperinsulinemia in mice, ..
  29. Walter J Lukiw; Fiscal Year: 2016
    ..Down-regulated TSPAN12 restricts ADAM10 (a-secretase) dependent cleavage of beta-amyloid precursor protein ([unreadable]APP)...
  30. Adipose Tissue Amyloid Precursor Protein and Beta-Amyloid
    William G Tharp; Fiscal Year: 2013
    ..Altered processing of Amyloid Precursor Protein (APP) leads to increased neuronal production of pathologic amyloid-b (Ab) fragments, which is a major ..
  31. Effects of bladder control medication on beta-amyloid peptide metabolism
    Jeremy B Tuttle; Fiscal Year: 2012
    ..Scopolamine increases AD pathology in human brains and in the Tg2576 AD-like mouse. This mouse carries a mutated APP(swe) that causes a familial form of AD...
  32. Xinmin Simon Xie; Fiscal Year: 2014
    ..efficacy (neurobehavioral and neuropathological outcomes) of lead compounds by oral administration to the AD model APP/PS1 mice...
  33. Izumi Maezawa; Fiscal Year: 2016
    ..A protein deposited in AD brains called amyloid-beta (Abeta) has been hypothesized to play a critical role in AD pathogenesis...
  34. Development of a HTS assay for modulators of presenilin 1 conformation
    Oksana Berezovska; Fiscal Year: 2010
    ..The final enzymatic step in generating Ass via cleavage of the amyloid precursor protein (APP) is performed by the presenilin 1 (PS1) dependent ?-secretase complex...
  35. SALLY ANN FRAUTSCHY; Fiscal Year: 2015
    ..from turmeric root, a combination which we have found to work synergistically and has shown large benefits in APP and tau models, but not tested in relation to ApoE isoform...
  36. Zoran Brkanac; Fiscal Year: 2015
    ..Mutations in the APP, PSEN1 or PSEN2 genes are involved in minority of AD families and are characterized with early disease onset...
  37. Cellular Cofactors, Neuronal Stress & Rescue, Aging & Alzheimer Disease
    Shi Du Yan; Fiscal Year: 2010
    ..on neuronal stress by cross-breeding homozygous RAGE null mice with transgenic (Tg) mice overexpressing mutant APP (Tg mAPP), and by a decoy receptor, soluble RAGE...
  38. Guojun Bu; Fiscal Year: 2016
    ..out in the background of apoE3-targeted replacement (TR) mice or apoE4-TR mice, without or with amyloid model APP/PS1 background...
  39. Identifying Alzheimer's disease genes using genomic and family data
    ELIZABETH MARCHANI BLUE; Fiscal Year: 2012
    ..As a postdoctoral fellow, she has recently published evidence that several genes in addition to APP, PSEN1, PSEN2, and APOE influence Alzheimer's disease...
  40. ELIZABETH MARCHANI BLUE; Fiscal Year: 2016
    ..As a postdoctoral fellow, she has recently published evidence that several genes in addition to APP, PSEN1, PSEN2, and APOE influence Alzheimer's disease...
  41. Insulin/Insulin receptor modulate APP phosphorylation and dementia
    LUCIANO D'ADAMIO; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Processing of the amyloid precursor protein (APP) is firmly associated with the pathogenesis of Alzheimer's disease (AD)...
  42. Spatial and temporal progression of amyloid angiopathy
    Matthew P Frosch; Fiscal Year: 2010
    ..characteristics of CAA and our access to a wide range of human samples (including sporadic CAA, CAA linked to APP mutations, tissue from the AN1792 trial of the Aft vaccine and familial British and Danish dementias...
  43. Single Molecule Approach to Neurodegeneration in Alzheimer's Disease
    Ari Gafni; Fiscal Year: 2010
    ..Aim 2: To determine the mechanism of Abeta oligomer assembly on the surface of membranes from neuronal cells, characterize the size of the oligomers at the ..
  44. Salvatore Oddo; Fiscal Year: 2015
    ..The identification of the pathways that lead to cognitive decline may point to new therapeutic targets. ..
  45. ABeta degrading enzyme and mitochondrial function
    Shidu Yan; Fiscal Year: 2012
    ..A[unreadable] progressively accumulates in the mitochondria of AD brain and transgenic mutant amyloid precursor protein (mAPP) mice overexpressing A[unreadable], which is linked to mitochondrial and neuronal malfunction in ..
  46. Alzheimers Disease Mechanism & Experimental Therapeutic
    Philip Wong; Fiscal Year: 2009
    ..of the elderly, is a progressive neurodegenerative disorder characterized by the deposition of amyloid-beta (Abeta) and neurofibrillary tangles in the brain...
  47. Protein-Protein Interactions in the Biology of Beta-APP
    Dennis J Selkoe; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Studies from many laboratories now generally support the amyloid (or Abeta) hypothesis of Alzheimer's disease (AD), and therapeutic trails based on this concept have begun...
  48. Pathologic protein folding and human disease
    David B Teplow; Fiscal Year: 2010
    ..In AD, the amyloid beta-protein (Abeta) self-associates to form oligomeric structures that circulate in plasma and cerebrospinal fluid...
  49. LRP/RanBP9 Pathway in Alzheiimer's Disease Pathogenesis
    David E Kang; Fiscal Year: 2011
    ..the LRP-C37 domain and its interacting proteins, in particular RanBP9, play important roles in APP trafficking and Abeta generation...
  50. Huilin Li; Fiscal Year: 2015
    ..gamma-Secretase was originally identified as the protease affecting the final scission of APP to release amyloid beta-protein, which is causally implicated in Alzheimer's disease (AD)...
  51. Pathologic Interactions of Amyloid Beta-Protein
    William E Van Nostrand; Fiscal Year: 2011
    ..We will utilize a combination of biochemical, molecular, ultrastructural, and cell culture approaches to understand these interactions and the consequences of them. ..
  52. Paul H Axelsen; Fiscal Year: 2016
    ....
  53. APP INTERNALIZATION--PREREQUISITE FOR ABETA FORMATION?
    Edward Koo; Fiscal Year: 2000
    ..of Alzheimer's disease, a process that may be related to altered expression or processing of the amyloid precursor protein (APP)...
  54. FUNCTION OF AN APP CYTOPLASMIC DOMAIN BINDING PROTEIN
    I Shapiro; Fiscal Year: 1999
    ..Normal cells process APP, alternately, into secreted amyloid beta-protein (Abeta), or into a secreted form cleaved in the middle of the Abeta domain (APPsalpha), or degrade APP completely within ..
  55. MICHAEL THOMAS BOWERS; Fiscal Year: 2016
    ..No abstract provided ..
  56. KATHLEEN RAMAN; Fiscal Year: 2016
    ..Aortic wall inflammation results in two fundamental structural changes which underlie AAA;elastin degradation and loss of smooth muscle cells (SMC) within the aortic media...
  57. Regulation of Leukocyte Migration by Plasminogen
    JANE LEE HOOVER-PLOW; Fiscal Year: 2013
    ..Utilizing Plg deficient (Plg-/-) mice in peritonitis and abdominal aortic aneurysm (AAA) models, our studies provide in vivo evidence that Plg/plasmin is required for macrophage recruitment and this role ..
  58. Syndecan-1 in Aortic Aneurysm Formation
    Elliot Chaikof; Fiscal Year: 2012
    ..heparan sulfate proteoglycan syndecan-1 may provide an important mechanism that inhibits abdominal aortic aneurysm (AAA) formation by limiting proteolytic or inflammatory activity and by promoting local reparative responses...
  59. Correlation of MMP activity with anatomic changes in the ruptured AAA wall
    SEAN JASON ENGLISH; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Abdominal aortic aneurysm (AAA) is a lethal disease, with significant public health ramifications as the population ages. AAA rupture is associated with a uniformly high mortality rate (80%)...
  60. Huaxi Xu; Fiscal Year: 2016
    ..A? peptides are derived from ?-amyloid precursor protein (APP) through sequential cleavages by ?-secretase and ?-secretase...
  61. Kurt R Brunden; Fiscal Year: 2014
    ..2FIII, binds to the thromboxane A2 (TP) receptor on neurons and causes an increase in expression of the amyloid precursor protein (APP) from which A is derived...
  62. Testing cell autonomy of AD phenotypes using human IPS cells
    Lawrence S Goldstein; Fiscal Year: 2013
    ..all FAD and SAD neuronal misbehavior is solely the result of processes initiated or enhanced by secreted Amyloid Precursor Protein (APP) fragments such as A[unreadable] and sAPP (and therefore cell non-autonomous), or whether A[..
  63. Discovery metabolite profiling of the prolyl peptidases
    Alan Saghatelian; Fiscal Year: 2009
    ..Furthermore, the application of DMP to peptidases will demonstrate the generality of this approach for the future characterization of medically relevant enzymes and signaling pathways. ..
  64. Alzheimer Vaccines: Noninvasive Vaccination by DNA-Base*
    Ken Ichiro Fukuchi; Fiscal Year: 2005
    ..AD and IBM share a number of common pathologies. For example, patients with AD develop amyloid beta-protein (Abeta) deposits and neurofibrillary tangles mainly composed of paired helical filaments (PHF) in brain, while patients ..
  65. BETAAPP MODULATION BY THE ADAPTER PROTEINS FE65 AND X11
    Efrat Levy; Fiscal Year: 2003
    DESCRIPTION (From the applicant's abstract): Beta-amyloid precursor protein (Beta-APP) is an integral transmembrane glycoprotein whose proteolytic processing results in the generation and secretion of soluble Beta-APP amino-terminal ..
  66. Cell Models for Alzheimer's disease (AD): Lipids and Related Signaling Pathways
    Grace Y Sun; Fiscal Year: 2012
    ..microvessels through transactivation of integrins and growth factor receptors, and P2Y2Rs mediate neuroprotective APP processing by a different pathway than inflammation;and (3) statins have both cholesterol-independent and -..
  67. Cynthia A Lemere; Fiscal Year: 2014
    ..C3 and its receptor CR3 also mediate microglial uptake and degradation of amyloid-beta (Abeta), a key protein in AD...
  68. Giulio Taglialatela; Fiscal Year: 2016
    ..team of experts in neuronal molecular signaling in AD (Taglialatela), CNS electron microscopy (Carlton), behavior in APP Tg mouse models (Dineley), proteomics (Wiktorowicz), AD histopathology (Woltjer) and AD clinical aspects (Quinn).
  69. Huntington Potter; Fiscal Year: 2015
    ..Previously, we found that in AD patients, tg mice, and cultured cells, mutant amyloid precursor protein and presenilin genes that cause familial AD induce chromosome mis-segregation and aneuploidy, processes ..
  70. Lennart Mucke; Fiscal Year: 2016
    ..Transgenic mice with neuronal expression of familial AD-mutant forms of the human amyloid precursor protein (hAPPFAD mice), which simulate several aspects of AD, had increased neuronal DSBs at baseline and more ..
  71. Gopal Thinakaran; Fiscal Year: 2015
    ..by the cerebral deposition of ?-amyloid peptides (A?), generated by sequential proteolysis of amyloid precursor protein (APP) by BACE1 and ?-secretase...
  72. Erhard Bieberich; Fiscal Year: 2016
    ..Using a combination of in vitro and in vivo models (Psen1 and APP/PS1 astrocytes and mice);our study will develop a novel strategy to protect astrocytes and neurons from apoptosis...
  73. Proteoglycans/Glycosaminoglycans in APP Transgenic Mice
    ALAN SNOW; Fiscal Year: 2004
    ..is characterized by the accumulation of insoluble fibrillar amyloid deposits containing the beta-amyloid protein (Abeta), either as extracellular amyloid plaques in the brain parenchyma or in blood vessel walls...
  74. Effect of RanbpM on amyloid pathology in a mouse model of Alzheimer's disease
    MADEPALLI KRISHNAPPA LAKSHMANA; Fiscal Year: 2009
    ..suggests that the low density lipoprotein receptor-related protein (LRP) facilitates amyloidogenic processing of APP. Within LRP, we defined the last 37 C-terminal residues of LRP (LRP-C37) lacking the NPxY or YxxL domains ..
  75. Transgenic Mice Depositing Individual AB peptides
    Eileen McGowan; Fiscal Year: 2006
    Title: Transgenic mice expressing individual Abeta peptides. Transgenic mouse models have been developed that deposit Abeta in the brain...
  76. APOLIPOPROTEIN AND AD AMYLOID FORMATION
    Xuemin Xu; Fiscal Year: 2001
    ..The present proposal is driven by the following hypotheses: (I) apolipoprotein E (apoE) interacts with amyloid precursor protein (APP) intracellularly; (II) both N-terminal and C-terminal domains of APP are involved in the ..
  77. Beta-Amyloid Aggregation and Toxicity:
    REGINA MURPHY; Fiscal Year: 2003
    ..The predominant protein component of the amyloid deposit is beta-amyloid (Abeta), a 4 kDa peptide derived from a much larger transmembrane precursor protein, deposited as insoluble fibrils of ..

Patents1

  1. Precursor protein of APC polypeptide, DNA coding therefor and diagnostic use of the DNA and protein
    Patent Number: EP0276723-A2; Date:1988-08-03