amyloid beta protein precursor

Summary

Summary: A precursor to the AMYLOID-BETA PROTEIN (beta/A4). Alterations in the expression of the amyloid beta-protein precursor (ABPP) gene, located on chromosome 21, plays a role in the development of the neuropathology common to both ALZHEIMER DISEASE and DOWN SYNDROME. ABPP is associated with the extensive extracellular matrix secreted by neuronal cells. Upon cleavage, this precursor produces three proteins of varying amino acid lengths: 695, 751, and 770. The beta/A4 (695 amino acids) or beta-amyloid protein is the principal component of the extracellular amyloid in senile plaques found in ALZHEIMER DISEASE; DOWN SYNDROME and, to a limited extent, in normal aging.

Top Publications

  1. ncbi Alzheimer's disease is a synaptic failure
    Dennis J Selkoe
    Center for Neurologic Diseases, Brigham and Women s Hospital, and the Harvard Center for Neurodegeneration and Repair, Boston, MA 02115, USA
    Science 298:789-91. 2002
  2. ncbi Alzheimer's disease: genes, proteins, and therapy
    D J Selkoe
    Department of Neurology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA
    Physiol Rev 81:741-66. 2001
  3. 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
  4. 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
  5. ncbi The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
    J Kang
    Nature 325:733-6. 1987
  6. pmc Macroautophagy--a novel Beta-amyloid peptide-generating pathway activated in Alzheimer's disease
    W Haung Yu
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY 10962, USA
    J Cell Biol 171:87-98. 2005
  7. ncbi Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease
    Jorge J Palop
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Neuron 55:697-711. 2007
  8. pmc Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts
    Robert Ehehalt
    Max Planck Institute of Molecular Cell Biology and Genetics, D 01307 Dresden, Germany
    J Cell Biol 160:113-23. 2003
  9. ncbi Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695
    M A Chishti
    Centre for Research in Neurodegenerative Diseases, The Department of Laboratory Medicine, Division of Neurology, University Health Network, University of Toronto, Toronto, Ontario M5S 3H2, Canada
    J Biol Chem 276:21562-70. 2001
  10. pmc Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology
    C Sturchler-Pierrat
    Novartis Pharma, Inc, Basel, Switzerland
    Proc Natl Acad Sci U S A 94:13287-92. 1997

Research Grants

  1. ROLES OF VASCULAR AMYLOID BETA PROTEIN PRECURSOR
    William Van Nostrand; Fiscal Year: 1999
  2. Effects of Statins on AD beyond Cholesterol and Amyloid
    Ling Li; Fiscal Year: 2006
  3. TRISOMY 16 AND NGF--EFFECTS ON CNS GENE EXPRESSION
    David Holtzman; Fiscal Year: 1993
  4. Acquiring robotic support for mass spectrometry core
    CRAIG MALBON; Fiscal Year: 2003
  5. AMYLOID ANGIOPATHY, EARLY PLAQUES & AGING
    Blas Frangione; Fiscal Year: 2003
  6. BIOCHEMISTRY AND BIOPHYSICS OF BPTI FOLDING MUTANTS
    Stephen Anderson; Fiscal Year: 1993
  7. The Role of Sortilin in Alzheimer's Disease
    GINA FINAN; Fiscal Year: 2009
  8. p75NTR proteolysis in Alzheimer's Disease
    Natalie Landman; Fiscal Year: 2006
  9. Structure and mechanism of signal peptide peptidase
    Michael S Wolfe; Fiscal Year: 2010
  10. The Role of Presenilin in Gamma-Secretase Activity
    Michael Wolfe; Fiscal Year: 2009

Detail Information

Publications262 found, 100 shown here

  1. ncbi Alzheimer's disease is a synaptic failure
    Dennis J Selkoe
    Center for Neurologic Diseases, Brigham and Women s Hospital, and the Harvard Center for Neurodegeneration and Repair, Boston, MA 02115, USA
    Science 298:789-91. 2002
    ....
  2. ncbi Alzheimer's disease: genes, proteins, and therapy
    D J Selkoe
    Department of Neurology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA
    Physiol Rev 81:741-66. 2001
    ..The progress reviewed here, coupled with better ability to diagnose the disease early, bode well for the successful development of therapeutic and preventative drugs for this major public health problem...
  3. 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
    ..Finally, the expression pattern and subcellular localization of BACE were consistent with that expected for beta-secretase. Future development of BACE inhibitors may prove beneficial for the treatment of Alzheimer's disease...
  4. 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
    ..Screening other cases of familial AD revealed a second unrelated family in which this variant occurs. This suggests that some cases of AD could be caused by mutations in the APP gene...
  5. 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...
  6. pmc Macroautophagy--a novel Beta-amyloid peptide-generating pathway activated in Alzheimer's disease
    W Haung Yu
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY 10962, USA
    J Cell Biol 171:87-98. 2005
    ..Our results, therefore, link beta-amyloidogenic and cell survival pathways through macroautophagy, which is activated and is abnormal in AD...
  7. ncbi Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease
    Jorge J Palop
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Neuron 55:697-711. 2007
    ..Aberrant increases in network excitability and compensatory inhibitory mechanisms in the hippocampus may contribute to Abeta-induced neurological deficits in hAPP mice and, possibly, also in humans with AD...
  8. pmc Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts
    Robert Ehehalt
    Max Planck Institute of Molecular Cell Biology and Genetics, D 01307 Dresden, Germany
    J Cell Biol 160:113-23. 2003
    ..Thus, access of alpha- and beta-secretase to APP, and therefore A beta generation, may be determined by dynamic interactions of APP with lipid rafts...
  9. ncbi Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695
    M A Chishti
    Centre for Research in Neurodegenerative Diseases, The Department of Laboratory Medicine, Division of Neurology, University Health Network, University of Toronto, Toronto, Ontario M5S 3H2, Canada
    J Biol Chem 276:21562-70. 2001
    ..The Tg mice described here suggest a potential to investigate aspects of Alzheimer's disease pathogenesis, prophylaxis, and therapy within short time frames...
  10. pmc Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology
    C Sturchler-Pierrat
    Novartis Pharma, Inc, Basel, Switzerland
    Proc Natl Acad Sci U S A 94:13287-92. 1997
    ..These mice resemble major features of AD pathology and suggest a central role of A beta in the pathogenesis of the disease...
  11. 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
    ..This mutation occurs at the amino terminal of beta-amyloid and may be pathogenic because it occurs at or close to the endosomal/lysosomal cleavage site of the molecule. Thus, pathogenic mutations in APP frame the beta-amyloid sequence...
  12. 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
    ....
  13. ncbi In vitro phosphorylation of the cytoplasmic domain of the amyloid precursor protein by glycogen synthase kinase-3beta
    A E Aplin
    Department of Neuroscience, Institute of Psychiatry, London, England
    J Neurochem 67:699-707. 1996
    ..The ability of GSK-3beta to phosphorylate APPcyt and tau provides a putative link between the two lesions and indicates a critical role of GSK-3beta in the pathogenesis of Alzheimer's disease...
  14. ncbi Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein
    B De Strooper
    Experimental Genetics Group, Flemish Institute for Biotechnology VIB4, Center for Human Genetics, K U Leuven, Belgium
    Nature 391:387-90. 1998
    ..Our results indicate that mutations in PS1 that manifest clinically cause a gain of function and that inhibition of PS1 activity is a potential target for anti-amyloidogenic therapy in Alzheimer's disease...
  15. ncbi Identification of a novel aspartic protease (Asp 2) as beta-secretase
    I Hussain
    Department of Neurosciences, SmithKline Beecham Pharmaceuticals, Harlow, Essex, United Kingdom
    Mol Cell Neurosci 14:419-27. 1999
    ..Asp 2 localizes to the Golgi/endoplasmic reticulum in transfected cells and shows clear colocalization with APP in cells stably expressing the 751-amino-acid isoform of APP...
  16. pmc Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein
    X Lin
    Protein Studies Program, Oklahoma Medical Research Foundation, and Department of Biochemistry, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
    Proc Natl Acad Sci U S A 97:1456-60. 2000
    ..Alignment of cleavage site sequences of peptides indicates that the specificity of memapsin 2 resides mainly at the S(1)' subsite, which prefers small side chains such as Ala, Ser, and Asp...
  17. pmc The Alzheimer amyloid precursor protein (APP) and FE65, an APP-binding protein, regulate cell movement
    S L Sabo
    Laboratory of Molecular and Cellular Neuroscience and the Zachary and Elizabeth M Fisher Center, The Rockefeller University, New York, New York 10021, USA
    J Cell Biol 153:1403-14. 2001
    ..These data are consistent with a role for FE65 and APP, possibly in a Mena-containing macromolecular complex, in regulation of actin-based motility...
  18. ncbi Neprilysin gene transfer reduces human amyloid pathology in transgenic mice
    Robert A Marr
    Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    J Neurosci 23:1992-6. 2003
    ..These data further support a role for neprilysin in regulating cerebral amyloid deposition and suggest that gene transfer approaches might have potential for the development of alternative therapies for Alzheimer's disease...
  19. ncbi Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities
    Alena Savonenko
    Department of Pathology, Johns Hopkins School of Medicine, Ross Building, Room 558, 720 Rutland Avenue, Baltimore, MD 21205, USA
    Neurobiol Dis 18:602-17. 2005
    ....
  20. ncbi Soluble form of amyloid precursor protein regulates proliferation of progenitors in the adult subventricular zone
    Isabelle Caille
    CNRS UMR 8542, Ecole Normale Superieure, 46 rue d Ulm, 75005 Paris, France
    Development 131:2173-81. 2004
    ..These results reveal a new function for sAPP as a regulator of SVZ progenitor proliferation in the adult central nervous system...
  21. ncbi The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer's disease
    D J Selkoe
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
    Trends Cell Biol 8:447-53. 1998
    ..This review discusses the current understanding of the cell biology of two proteins crucial for the pathogenesis of AD, the beta-amyloid precursor protein and presenilin...
  22. ncbi Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death
    Malcolm A Leissring
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Harvard Medical School, Boston, MA 02115, USA
    Neuron 40:1087-93. 2003
    ..Our findings demonstrate that chronic upregulation of Abeta-degrading proteases represents an efficacious therapeutic approach to combating Alzheimer-type pathology in vivo...
  23. pmc Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy
    Tara L Spires
    Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurosci 25:7278-87. 2005
    ..Decreased spine density will likely contribute to altered neural system function and behavioral impairments observed in Tg2576 mice...
  24. ncbi BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics
    S L Roberds
    Department of Genomics, Pharmacia Corp, 301 Henrietta Street, Kalamazoo, MI 49007, USA
    Hum Mol Genet 10:1317-24. 2001
    ....
  25. ncbi A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain
    B De Strooper
    Neuronal Cell Biology and Gene Transfer Laboratory, Flanders Institute for Biotechnology VIB4, Center for Human Genetics, KU Leuven, Belgium
    Nature 398:518-22. 1999
    ..Thus the targeting of gamma-secretase for the treatment of Alzheimer's disease may risk toxicity caused by reduced Notch signalling...
  26. ncbi Regulation of NMDA receptor trafficking by amyloid-beta
    Eric M Snyder
    Laboratory for Molecular and Cellular Neuroscience, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nat Neurosci 8:1051-8. 2005
    ..Dephosphorylation of the NMDA receptor subunit NR2B at Tyr1472 correlated with receptor endocytosis. These data indicate a new mechanism by which amyloid-beta can cause synaptic dysfunction and contribute to Alzheimer disease pathology...
  27. pmc Homo- and heterodimerization of APP family members promotes intercellular adhesion
    Peter Soba
    ZMBH, University of Heidelberg, Heidelberg, Germany
    EMBO J 24:3624-34. 2005
    ..Together, our results provide evidence that homo- and heterocomplexes of APP/APLPs promote trans-cellular adhesion in vivo...
  28. ncbi APP processing and synaptic function
    Flavio Kamenetz
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Neuron 37:925-37. 2003
    ..Disruption of this feedback system could contribute to disease progression in AD...
  29. ncbi Reversible memory loss in a mouse transgenic model of Alzheimer's disease
    Linda A Kotilinek
    Department of Neurology, University of Minnesota, Minneapolis 55455, USA
    J Neurosci 22:6331-5. 2002
    ..If these Abeta assemblies contribute significantly to memory loss in AD, then successfully targeting them might improve memory in some AD patients...
  30. 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
    ..The binding of X11 or FE65 PI domains to residues of the YENPTY motif of (beta)APP identifies PI domains as general protein interaction domains and may have important implications for the processing of (beta)APP...
  31. ncbi A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity
    S Weggen
    Department of Neurosciences, University of California San Diego, La Jolla, California 92093, USA
    Nature 414:212-6. 2001
    ....
  32. ncbi A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltransferase Tip60
    X Cao
    The Center for Basic Neuroscience, Department of Molecular Genetics, and Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390 9111 USA
    Science 293:115-20. 2001
    ..This complex potently stimulates transcription via heterologous Gal4- or LexA-DNA binding domains, suggesting that release of the cytoplasmic tail of APP by gamma-cleavage may function in gene expression...
  33. ncbi Interaction of Alzheimer's beta -amyloid precursor family proteins with scaffold proteins of the JNK signaling cascade
    Hidenori Taru
    Laboratory of Neurobiophysics, School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    J Biol Chem 277:20070-8. 2002
    ..Analysis of APP family proteins and their associated proteins is expected to contribute to understanding the molecular process of neural degeneration in Alzheimer's disease...
  34. ncbi High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation
    L Mucke
    Gladstone Institute of Neurological Disease, Department of Neurology, and Neuroscience Program, University of California, San Francisco, California 94141 9100, USA
    J Neurosci 20:4050-8. 2000
    ..Our results support the emerging view that plaque-independent Abeta toxicity plays an important role in the development of synaptic deficits in AD and related conditions...
  35. ncbi Purification and cloning of amyloid precursor protein beta-secretase from human brain
    S Sinha
    Elan Pharmaceuticals, South San Francisco, California 94080, USA
    Nature 402:537-40. 1999
    ..Cloning and expression of the enzyme reveals that human brain beta-secretase is a new membrane-bound aspartic proteinase...
  36. ncbi The secreted beta-amyloid precursor protein ectodomain APPs alpha is sufficient to rescue the anatomical, behavioral, and electrophysiological abnormalities of APP-deficient mice
    Sabine Ring
    Department of Bioinformatics and Functional Genomics, Institute for Pharmacy and Molecular Biotechnology, University of Heidelberg, D 69120 Heidelberg, Germany
    J Neurosci 27:7817-26. 2007
    ..Together, our data suggest that the APP C terminus is dispensable and that APPs alpha is sufficient to mediate the physiological functions of APP assessed by these tests...
  37. ncbi A vector for expressing foreign genes in the brains and hearts of transgenic mice
    D R Borchelt
    Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21205 2196, USA
    Genet Anal 13:159-63. 1996
    ..The MoPrP.Xho vector should be very useful in strategies designed to overexpress a variety of wild-type and disease related mutant transgenes in the heart and brain...
  38. ncbi Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP
    A Kamal
    Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093 0683, USA
    Nature 414:643-8. 2001
    ....
  39. ncbi Time course of the development of Alzheimer-like pathology in the doubly transgenic PS1+APP mouse
    Marcia N Gordon
    Alzheimer Research Laboratory, Department of Pharmacology, University of South Florida, Tampa, Florida 33612 4799, USA
    Exp Neurol 173:183-95. 2002
    ....
  40. ncbi Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease
    Gorazd B Stokin
    Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego UCSD, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Science 307:1282-8. 2005
    ..Reductions in microtubule-dependent transport may stimulate proteolytic processing of beta-amyloid precursor protein, resulting in the development of senile plaques and Alzheimer's disease...
  41. ncbi Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein
    D Games
    Athena Neurosciences, Inc, South San Francisco, California 94080
    Nature 373:523-7. 1995
    ..These mice support a primary role for APP/A beta in the genesis of AD and could provide a preclinical model for testing therapeutic drugs...
  42. ncbi An iron-responsive element type II in the 5'-untranslated region of the Alzheimer's amyloid precursor protein transcript
    Jack T Rogers
    Genetics and Aging Research Unit, Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts 02129 4404, USA
    J Biol Chem 277:45518-28. 2002
    ....
  43. ncbi Chronic stress accelerates learning and memory impairments and increases amyloid deposition in APPV717I-CT100 transgenic mice, an Alzheimer's disease model
    Yun Ha Jeong
    Department of Pharmacology, College of Medicine, National Creative Research Initiative Centre for Alzheimer s Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, Korea
    FASEB J 20:729-31. 2006
    ....
  44. 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
    ..Our data suggest that transcriptional transactivation by APP and Notch may involve distinct mechanisms; whereas the Notch intracellular domain directly functions in the nucleus, the AICD acts indirectly by activating Fe65...
  45. ncbi Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice
    C S von Koch
    Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 2196, USA
    Neurobiol Aging 18:661-9. 1997
    ..Adult double KO mice mate poorly, despite apparent normal ovarian and testicular development. Otherwise, double KO mice appear healthy up to 13 months of age. We conclude, that APLP2 and APP can substitute for each other functionally...
  46. ncbi Mutagenesis identifies new signals for beta-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Abeta42
    R G Perez
    Departments of Psychiatry and Neurobiology and Anatomy, Allegheny University of the Health Sciences, Pittsburgh, Pennsylvania 15212, USA
    J Biol Chem 274:18851-6. 1999
    ....
  47. ncbi Transcriptional and translational regulation of BACE1 expression--implications for Alzheimer's disease
    Steffen Rossner
    Paul Flechsig Institute for Brain Research, Department of Neurochemistry, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany
    Prog Neurobiol 79:95-111. 2006
    ....
  48. ncbi Compartmentalization of beta-secretase (Asp2) into low-buoyant density, noncaveolar lipid rafts
    D R Riddell
    Neurology Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow CM19 5AW, United Kingdom
    Curr Biol 11:1288-93. 2001
    ..These observations are consistent with the raft localization of APP processing and suggest that the partitioning of Asp2 into lipid rafts may underlie the cholesterol sensitivity of beta-amyloid production...
  49. ncbi Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory
    Paul R Turner
    Department of Biochemistry, University of Otago, Dunedin, New Zealand
    Prog Neurobiol 70:1-32. 2003
    ..To this end, there is an urgent need for a dedicated research effort aimed at understanding the behavioral consequences of altered levels and activity of the different APP fragments as a result of experience and disease...
  50. ncbi Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2
    Pei Wang
    Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, USA
    J Neurosci 25:1219-25. 2005
    ..Our results identify APP/APLP2 as key regulators of structure and function of developing neuromuscular synapses...
  51. pmc Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations
    A M Cataldo
    Nathan S Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA
    Am J Pathol 157:277-86. 2000
    ....
  52. pmc A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model
    Rolf Postina
    Institute of Biochemistry, University of Mainz, Mainz, Germany
    J Clin Invest 113:1456-64. 2004
    ....
  53. pmc Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production
    Tobias Moehlmann
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    Proc Natl Acad Sci U S A 99:8025-30. 2002
    ..Finally, we show that PS1 L166 mutants affect the generation of NICD and AICD in a similar manner, supporting the concept that S3 protease and S3-like gamma-secretase cleavages are mediated by identical proteolytic activities...
  54. ncbi Axonal transport, amyloid precursor protein, kinesin-1, and the processing apparatus: revisited
    Orly Lazarov
    Department of Neurobiology, Pharmacology, and Physiology, The University of Chicago, Chicago, Illinois 60637, USA
    J Neurosci 25:2386-95. 2005
    ....
  55. ncbi Age-dependent neurodegeneration and Alzheimer-amyloid plaque formation in transgenic Drosophila
    Isabell Greeve
    Center for Molecular Neurobiology, University of Hamburg, 20251 Hamburg, Germany
    J Neurosci 24:3899-906. 2004
    ..This invertebrate model of amyloid plaque pathology demonstrates Abeta-induced neurodegeneration as a basic biological principle and may allow additional genetic analyses of the underlying molecular pathways...
  56. 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
    ....
  57. pmc BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein
    M Farzan
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 97:9712-7. 2000
    ..These data suggest that BACE2 contributes to Abeta production in individuals bearing the Flemish mutation, and that selective inhibition of these highly similar proteases may be feasible and therapeutically advantageous...
  58. ncbi High levels of Alzheimer beta-amyloid precursor protein (APP) in children with severely autistic behavior and aggression
    Deborah K Sokol
    Department of Neurology, Indiana University School of Medicine, 702 Barnhill Drive, Indianapolis, IN 46202, USA
    J Child Neurol 21:444-9. 2006
    ..This favors an increased alpha-secretase pathway in autism (anabolic), opposite to what is seen in Alzheimer disease. Additionally, a complex relationship between age, acetylcholinesterase, and plasma neuronal markers was found...
  59. ncbi Gene knockout of amyloid precursor protein and amyloid precursor-like protein-2 increases cellular copper levels in primary mouse cortical neurons and embryonic fibroblasts
    Shayne A Bellingham
    Department of Genetics, The University of Melbourne, Victoria, Australia
    J Neurochem 91:423-8. 2004
    ....
  60. 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
    ..The in vivo findings that AICD can contribute to AD pathology independently of Abeta have important therapeutic implications and may explain some observations that are discordant with the amyloid hypothesis...
  61. ncbi Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein
    M Trommsdorff
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75235 9046, USA
    J Biol Chem 273:33556-60. 1998
    ....
  62. ncbi Age related changes in brain metabolites observed by 1H MRS in APP/PS1 mice
    Johanna Oberg
    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 14186 Stockholm, Sweden
    Neurobiol Aging 29:1423-33. 2008
    ..First differences in metabolite content were readily seen at 2.5 months, when volume defects in tg mice were present, but no amyloid plaques...
  63. ncbi The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production
    Lucia Pastorino
    Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Nature 440:528-34. 2006
    ..These findings provide new insight into the pathogenesis and treatment of Alzheimer's disease...
  64. ncbi Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity
    R Yan
    Cell and Molecular Biology, Pharmacia and Upjohn, Inc, Kalamazoo, MI 49007, USA
    Nature 402:533-7. 1999
    ..Thus, Asp2 is a new protein target for drugs that are designed to block the production of amyloid beta-peptide peptide and the consequent formation of amyloid plaque in Alzheimer's disease...
  65. ncbi Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients
    F W Van Leeuwen
    Graduate School for Neurosciences Amsterdam, Netherlands Institute for Brain Research, 1105 AZ Amsterdam, The Netherlands
    Science 279:242-7. 1998
    ..This type of transcript mutation is likely an important factor in the widely occurring nonfamilial early- and late-onset forms of Alzheimer's disease...
  66. pmc Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1
    Qiang Liu
    Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA
    Neuron 56:66-78. 2007
    ....
  67. pmc CD147 is a regulatory subunit of the gamma-secretase complex in Alzheimer's disease amyloid beta-peptide production
    Shuxia Zhou
    Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 102:7499-504. 2005
    ....
  68. ncbi Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo
    D R Borchelt
    Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Neuron 17:1005-13. 1996
    ..These studies provide compelling support for the view that one mechanism by which these mutant PS1 cause AD is by increasing the extracellular concentration of Abeta peptides terminating at 42(43), species that foster Abeta deposition...
  69. ncbi Inhibition of Abeta production and APP maturation by a specific PKA inhibitor
    Yuan Su
    Neuroscience Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA
    FEBS Lett 546:407-10. 2003
    ..Our data suggests that PKA plays an important role in the maturation of APP associated with APP processing...
  70. ncbi Characterization of a presenilin-mediated amyloid precursor protein carboxyl-terminal fragment gamma. Evidence for distinct mechanisms involved in gamma -secretase processing of the APP and Notch1 transmembrane domains
    C Yu
    Department of Neurobiology, Pharmacology and Physiology, The University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 276:43756-60. 2001
    ....
  71. pmc Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury
    Christine L Mac Donald
    Department of Biomedical Engineering, Washington University, St Louis, Missouri 63130, USA
    J Neurosci 27:11869-76. 2007
    ..Remarkably, DTI changes strongly predicted the approximate time since trauma. These results provide an important validation of DTI for pericontusional TAI and suggest novel clinical and forensic applications...
  72. pmc Regulation of amyloid precursor protein processing by the Beclin 1 complex
    Philipp A Jaeger
    Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, United States of America
    PLoS ONE 5:e11102. 2010
    ..Together, our findings suggest that autophagy and the BECN1-PIK3C3 complex regulate APP processing and play an important role in AD pathology...
  73. pmc Interruption of beta-catenin signaling reduces neurogenesis in Alzheimer's disease
    Ping He
    Haldeman Laboratory of Molecular and Cellular Neurobiology, Sun Health Research Institute, Sun City, Arizona 85351, USA
    J Neurosci 29:6545-57. 2009
    ..Similar results were observed in GPCs isolated from AD transgenic mice. These results suggest that Abeta-induced interruption of beta-catenin signaling may contribute to the impairment of neurogenesis in AD progenitor cells...
  74. ncbi beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity
    H Zheng
    Department of Genetics and Molecular Biology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    Cell 81:525-31. 1995
    ..In addition, four out of six homozygous mice showed reactive gliosis at 14 weeks of age, suggesting an impaired neuronal function as a result of the APP-null mutation...
  75. ncbi Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members
    S Heber
    Department of Neurochemistry, Max Planck Institute for Brain Research, D 60528 Frankfurt, Germany
    J Neurosci 20:7951-63. 2000
    ..Moreover, cortical neurons from single or combined mutant mice showed unaltered survival rates under basal culture conditions and unaltered susceptibility to glutamate excitotoxicity in vitro...
  76. 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 alternative APP mRNA is present in both brain and peripheral tissues of normal individuals and those with Alzheimer's disease, but its pattern of expression differs from that of the previously reported APP mRNA...
  77. ncbi Facilitation of stress-induced phosphorylation of beta-amyloid precursor protein family members by X11-like/Mint2 protein
    Hidenori Taru
    Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita Ku Kita 12 Nishi 6, Sapporo 060 0812, Japan
    J Biol Chem 279:21628-36. 2004
    ....
  78. ncbi A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's amyloid precursor protein beta-secretase
    A Solans
    Down Syndrome Research Group, Medical and Molecular Genetics Center, IRO, Hospital Duran i Reynals, Barcelona, Spain
    Cytogenet Cell Genet 89:177-84. 2000
    ..BACE2 could be involved in the Alzheimer-like neuropathology of Down syndrome, as well as in Alzheimer's disease linked to chromosome 21 but not showing mutations in APP...
  79. ncbi Constitutive alpha-secretase cleavage of the beta-amyloid precursor protein in the furin-deficient LoVo cell line: involvement of the pro-hormone convertase 7 and the disintegrin metalloprotease ADAM10
    E Lopez-Perez
    IPMC du CNRS, UMR6097, Valbonne, France
    J Neurochem 76:1532-9. 2001
    ..Transfection analysis allowed us to further establish that the pro-hormone convertase 7 and ADAM10 but not ADAM17 (TACE, tumour necrosis factor alpha-converting enzyme) likely contribute to constitutive sAPPalpha secretion by LoVo cells...
  80. pmc Take five--BACE and the gamma-secretase quartet conduct Alzheimer's amyloid beta-peptide generation
    Christian Haass
    Department of Biochemistry, Adolf Butenandt Institute, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, Munchen, Germany
    EMBO J 23:483-8. 2004
    ..It now appears that one needs to Take Five genes to produce a deadly peptide by a proteolytic mechanism, which paradoxically is otherwise of pivotal importance for development and cell fate decisions...
  81. 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
    ..These observations suggest that the phosphorylated form of APP may play an important role in neurite outgrowth of differentiating neurons...
  82. ncbi Animal models of Alzheimer's disease and frontotemporal dementia
    Jürgen Götz
    Alzheimer s and Parkinson s Disease Laboratory, Brain and Mind Research Institute, University of Sydney, 100 Mallett Street, Camperdown, NSW 2050, Australia
    Nat Rev Neurosci 9:532-44. 2008
    ..With advanced imaging techniques that can be used in both humans and mice an early, preclinical diagnosis of AD and FTD could be within reach...
  83. ncbi A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth
    D H Small
    Department of Pathology, University of Melbourne, Parkville, Victoria, Australia
    J Neurosci 14:2117-27. 1994
    ..The results indicate that the binding of APP to HSPG in the ECM may stimulate the effects of APP on neurite outgrowth...
  84. ncbi Rab5-stimulated up-regulation of the endocytic pathway increases intracellular beta-cleaved amyloid precursor protein carboxyl-terminal fragment levels and Abeta production
    Olivera M Grbovic
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA
    J Biol Chem 278:31261-8. 2003
    ..Our findings in this model system suggest that the endosomal pathology seen at the earliest stage of sporadic AD may contribute to APP proteolysis along a beta-amyloidogenic pathway...
  85. pmc Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury
    C L Mac Donald
    Department of Biomedical Engineering, Washington University, One Brookings Drive, Campus Box 1097, St Louis, MO 63110, USA
    Exp Neurol 205:116-31. 2007
    ..These results demonstrate that DTI is able to detect axonal injury, and support the hypothesis that DTI may be more sensitive than conventional imaging methods for this purpose...
  86. ncbi Beta-amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology
    J Apelt
    Paul Flechsig Institute for Brain Research, Department of Neurochemistry, University of Leipzig, Jahnallee 59, D 04109, Leipzig, Germany
    Brain Res 894:21-30. 2001
    ..The transgenic approach used in this study may thus provide a useful tool to further disclose the in vivo mechanisms by which pro- and anti-inflammatory cytokines interact and/or contribute to the progression of Alzheimer's disease...
  87. ncbi Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer's disease
    Joanna L Jankowsky
    Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 25:5217-24. 2005
    ..These results demonstrate that the generation of Abeta in vivo and its impact on the function of the nervous system can be strongly modulated by environmental factors...
  88. 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 propose that one of the normal functions of APP may be as a membrane cargo receptor for kinesin-I and that KLC is important for kinesin-I-driven transport of APP into axons...
  89. 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
    ..Our data demonstrate that APLPs and APP are processed similarly to act via the same nuclear target, suggesting that BACE 1 cleavage regulates a common function of APP and APLPs in neurons...
  90. 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
    ..We anticipate that this study will open the door to searches for markers of RIP signaling and surrogate markers for Abeta42 production...
  91. ncbi Targeting small Abeta oligomers: the solution to an Alzheimer's disease conundrum?
    W L Klein
    Northwestern University Institute for Neuroscience and Dept of Neurobiology and Physiology, Northwestern University, 2153 N Campus Drive, Evanston, IL 60208, USA
    Trends Neurosci 24:219-24. 2001
    ..Immuno-neutralization of soluble Abeta-derived toxins might be the key to optimizing AD vaccines that are now on the horizon...
  92. pmc Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease
    S Lammich
    Institut fur Biochemie, Johannes Gutenberg Universitat, Mainz, Becherweg 30, D 55128 Mainz, Germany
    Proc Natl Acad Sci U S A 96:3922-7. 1999
    ..Increases of its expression and activity might be beneficial for the treatment of Alzheimer's disease...
  93. 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...
  94. pmc Generation and initial characterization of FDD knock in mice
    Luca Giliberto
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA
    PLoS ONE 4:e7900. 2009
    ..The interaction between the two precursors, APP and BRI(2), and possibly between Abeta and ABri or ADan, could be important in influencing the rate of amyloid production or the tendency of these peptides to aggregate...
  95. ncbi Distinct intramembrane cleavage of the beta-amyloid precursor protein family resembling gamma-secretase-like cleavage of Notch
    Y Gu
    Department of Neuropathology, Faculty of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    J Biol Chem 276:35235-8. 2001
    ..This newly identified cleavage occurs at a site two to five residues inside the cytoplasmic membrane boundary, which is very similar to gamma-secretase-like cleavage of Notch 1...
  96. ncbi The neuronal adaptor protein X11alpha reduces Abeta levels in the brains of Alzheimer's APPswe Tg2576 transgenic mice
    Ju Hyun Lee
    Department of Neuroscience and Section of Old Age Psychiatry, The Institute of Psychiatry, Kings College, De Crespigny Park, Denmark Hill, London SE5 8AF, U K
    J Biol Chem 278:47025-9. 2003
    ..Thus, we report here the first demonstration that X11alpha inhibits Abeta production and deposition in vivo in the brain...
  97. ncbi Amyloidogenic processing of amyloid precursor protein: evidence of a pivotal role of glutaminyl cyclase in generation of pyroglutamate-modified amyloid-beta
    Holger Cynis
    Probiodrug AG, Weinbergweg 22, 06120 Halle Saale, Germany
    Biochemistry 47:7405-13. 2008
    ..The study provides new cell-based assays for the profiling of small molecule inhibitors of QC and points to conspicuous differences in processing of APP depending on sequence at the beta-secretase cleavage site...
  98. 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
    ..These results show that (1) PSEN1 and APP mutations account for 71% of ADEOAD families and (2) nonpenetrance at age <61 years is probably infrequent for PSEN1 or APP mutations...
  99. pmc BRI2 (ITM2b) inhibits Abeta deposition in vivo
    Jungsu Kim
    Department of Neuroscience, Mayo Clinic College of Medicine, Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA
    J Neurosci 28:6030-6. 2008
    ..These studies demonstrate that BRI2 is a novel mediator of Abeta deposition in vivo...
  100. ncbi The production of amyloid beta peptide is a critical requirement for the viability of central neurons
    Leigh D Plant
    School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Neurosci 23:5531-5. 2003
    ..Importantly, this toxicity, which our data suggest is a consequence of a decline in neuronal Abeta levels, was absent in non-neuronal cells. This study further supports a key physiological role for the enigmatic Abeta peptide...
  101. pmc Amyloid activates GSK-3beta to aggravate neuronal tauopathy in bigenic mice
    Dick Terwel
    Experimental Genetics Group, Department Human Genetics, Katholieke Universiteit Leuven Campus Gasthuisberg ON1 06 602, B 3000 Leuven, Belgium
    Am J Pathol 172:786-98. 2008
    ..The data indicate that amyloid induces tauopathy through activation of GSK-3 and suggest a role for the kinase in maintaining the functional integrity of adult neurons...

Research Grants63

  1. ROLES OF VASCULAR AMYLOID BETA PROTEIN PRECURSOR
    William Van Nostrand; Fiscal Year: 1999
    ..Better understanding of the biochemistry and cerebrovascular cell biology of PN- 2/AbetaPP will provide insight into its normal function as well as the patho-biochemistry and pathophysiology of this protein in certain disease states. ..
  2. Effects of Statins on AD beyond Cholesterol and Amyloid
    Ling Li; Fiscal Year: 2006
    ..abstract_text> ..
  3. TRISOMY 16 AND NGF--EFFECTS ON CNS GENE EXPRESSION
    David Holtzman; Fiscal Year: 1993
    Several neuronal genes expressed in the CNS, including the amyloid beta protein precursor (APP) have been assigned to human chromosome 21 (HSA 21)...
  4. Acquiring robotic support for mass spectrometry core
    CRAIG MALBON; Fiscal Year: 2003
    ..The institution has provided resources to enable the acquisition of two new mass spectrometers and this proposal builds on the investment. ..
  5. AMYLOID ANGIOPATHY, EARLY PLAQUES & AGING
    Blas Frangione; Fiscal Year: 2003
    ..Aim II: to construct, develop and characterize a transgenic mouse model for FBD. ..
  6. BIOCHEMISTRY AND BIOPHYSICS OF BPTI FOLDING MUTANTS
    Stephen Anderson; Fiscal Year: 1993
    ..lipoprotein-associated coagulation inhibitor and the alternatively-spliced domain of the Alzheimer's amyloid beta protein precursor. The overall basic thrust of the research has been to make genetically-modified forms of BPTI that ..
  7. The Role of Sortilin in Alzheimer's Disease
    GINA FINAN; Fiscal Year: 2009
    ..This is to be accomplished through a variety of techniques, some including: immunofluorescence, subcellular fractionation, RNAi, Western blot, and ELISA. ..
  8. p75NTR proteolysis in Alzheimer's Disease
    Natalie Landman; Fiscal Year: 2006
    ..Specific Aims are: 1) To examine the functional roles of p75-beta-p and p75-ICD fragments; 2) To determine the effects of PS mutations on proteolysis/signaling of the p75NTR. ..
  9. Structure and mechanism of signal peptide peptidase
    Michael S Wolfe; Fiscal Year: 2010
    ..A structure of SPP would provide tremendous insight into the workings of an unusual new class of enzymes that are critical to both biology and medicine. ..
  10. The Role of Presenilin in Gamma-Secretase Activity
    Michael Wolfe; Fiscal Year: 2009
    ..for substrate-protease recognition? (3) What is the role of Aph-1 and NCT in the assembly and activity of the protease complex? (4) How do mutations in PS that cause familial AD alter the specificity and activity of gamma-secretase? ..
  11. Determining Therapeutic Efficacy of AGE in AD
    Neelima Chauhan; Fiscal Year: 2005
    ..If successful, this project will validate the use of safe, naturally well-tolerated, cost-effective and alternative herbal pharmacotherapy for treating AD. ..
  12. PRESENILIN DOMAINS AND RECONSTITUTION OF CATALYSIS
    Samuel Gandy; Fiscal Year: 2007
    ..This investigation will permit the identification of the minimal functional unit for gamma-secretase activity and potentially support the notion that PS1 is indeed the catalytic component of the gamma-secretase complex. ..
  13. TRANSMITTER NEUROANATOMY IN ALZHEIMERS DISEASE
    Samuel Gandy; Fiscal Year: 2002
    ....
  14. Reduction of Amyloid Burden by Antisense APP
    Neelima Chauhan; Fiscal Year: 2005
    ..Significance: Targeting the translation of amyloidogenic APP by antisense synthetic oligodeoxynucleotides may prove to be an effective and safe form of gene therapy for treating familial AD and other genetic diseases. ..
  15. BABAA RECEPTORS IN AGING & ALZHEIMER'S DISEASE
    Samuel Gandy; Fiscal Year: 2002
    ....
  16. MOLECULAR MECHANISMS UNDERLYING GAP-43 FUNCTION
    Rachael Neve; Fiscal Year: 2001
    ..The data obtained from the proposed studies will begin to provide unifying molecular mechanisms for the diverse functions in which GAP-43 is known to participate. ..
  17. Interactive multiple gene expression map for the brain
    Kiminobu Sugaya; Fiscal Year: 2005
    ..Thus, we believe that our laboratory is uniquely, qualified to pursue this current proposal. ..
  18. Neuroreplacement strategies by mesenchymal stem cell
    Kiminobu Sugaya; Fiscal Year: 2007
    ..Thus, the proposed studies are expected to make a breakthrough in therapeutic strategies. ..
  19. FMRI in Pre-Symptomatic PS1-related Alzheimer's Disease
    John Ringman; Fiscal Year: 2005
    ..UCI, with its strong dementia research program, growing MRI capabilities and opportunity to collaborate at the nearby UCLA Brain Imaging Center, is an excellent environment for this endeavor. ..
  20. APP-BP1, The Cell Cycle, and Alzheimer Disease
    Rachael Neve; Fiscal Year: 2007
    ..We will test whether these predictions are correct. [unreadable] [unreadable]..
  21. LASER SCANNING CONFOCAL MICROSCOPE
    Ralph Nixon; Fiscal Year: 2005
    ....
  22. Small Molecule Drug Therapy for Parkinson's Disease
    Kiminobu Sugaya; Fiscal Year: 2008
    ..When successful, our drug candidate will offer a new treatment alternative for patients with neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and ALS. [unreadable] [unreadable] [unreadable]..
  23. The Biology of Alzheimer's Disease in Transgenic Mice
    Karen Ashe; Fiscal Year: 2008
    ..Abstract Not Provided. ..
  24. Modulating cognitive function in Tg2576 mice modeling AD
    Karen Ashe; Fiscal Year: 2006
    ..beta* causes cognitive impairment in Tg2576 and other mouse models of Alzheimer's disease. These results may provide important new information on the pathogenesis of dementia in Alzheimer's disease. ..
  25. Cerebral Microvascular Amyloid: Neuroinflammation and Cognitive Deficits
    William E Van Nostrand; Fiscal Year: 2010
    ....
  26. CaMKII and Neuronal Excitability Changes in Learning
    Masuo Ohno; Fiscal Year: 2007
    ..abstract_text> ..
  27. MLSN Screen of the PD Alpha Synuclein 5'UTR
    Jack Rogers; Fiscal Year: 2008
    ..Compounds directed to 5'UTRs of other mRNAs will probe mechanism of translation of the Abeta-amyloid precursor protein mRNA in Alzheimer's disease (SOD-1 mRNA in ALS, and PrP mRNA in Cruetzsfeld- Jacob Syndrome). [unreadable]..
  28. ETHANOL, INSULIN/IGF SIGNALING AND NEURONAL MIGRATION
    Suzanne de la Monte; Fiscal Year: 2008
    ..abstract_text> ..
  29. HTS Molecules Targeting APP 5'untranslated Region(RMI)
    Jack Rogers; Fiscal Year: 2007
    ..abstract_text> ..
  30. Genomic Search for Susceptibility to Alzheimer Disease
    Alison M Goate; Fiscal Year: 2010
    ..The use of case-control and endophenotype measures in CSF provides a powerful and novel approach to the genetics of LOAD. ..
  31. RNA Therapeutics and Abeta Precursor Protein Translation
    Jack Rogers; Fiscal Year: 2006
    ..Small molecules could well act by this pathway to decrease APP synthesis and concomitant ABeta-peptide output. ..
  32. Amyloid Beta Protein Precursor Influences Cerebral Thrombosis
    William E Van Nostrand; Fiscal Year: 2010
    ..This may lead to new avenues for developing strategies to regulate cerebral thrombosis and limit damage to the brain as a consequence of hemorrhagic and ischemic stroke. ..
  33. BETA AND ITS PRECURSOR INFLUENCE HEMOSTATIC ENZYMES
    William Van Nostrand; Fiscal Year: 2001
    ....
  34. ROLE OF PRESENILIN IN NOTCH AND APP MATURATION
    Alison Goate; Fiscal Year: 2003
    ..We also anticipate that these studies will increase our understanding of the Notch signaling, a process that is important not only for many developmental decisions but for cancer as well. ..
  35. APOE EFFECT ON CNS NEURONS--ROLE OF LRP
    David Holtzman; Fiscal Year: 2003
    ..These studies with physiological preparations of apoE as well as both in vivo and in vitro models should provide new insights into mechanisms underlying the link between apoE, LRP, ABeta, and Alzheimer's disease. ..
  36. CNS/plasma ABeta clearance of anti-ABeta antibody
    David Holtzman; Fiscal Year: 2003
    ..This will determine how anti-Abeta antibodies influence CNS/plasma Abeta transport exchanges. ..
  37. Microarrays for Alzheimer's Disease Mouse Models
    P Reddy; Fiscal Year: 2003
    ..The outcome of this proposed investigation will be useful in screening several mitochondrial antioxidants in AD transgenic mouse models as pre-clinical trials of AD patients...
  38. BIOSYNTHESIS OF ENKEPHALIN OPIOID PEPTIDES
    Vivian Hook; Fiscal Year: 2009
    ..These findings will enhance our knowledge of the complexity of the endogenous opioid system. ..
  39. Proteomics/Genomics of Opiate Analgesia and Addiction
    Vivian Hook; Fiscal Year: 2004
    ..Elucidation of distinct pathways will be significant, since it could allow future design of opiate drug regimens that provide effective analgesia, without the tolerance and dependence of addiction. ..
  40. AbetaPP and Cerebral Vasculopathy
    William Van Nostrand; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  41. INTEGRATED DNA SEQUENCING SYSTEM
    Vivian Hook; Fiscal Year: 2002
    ..abstract_text> ..
  42. Molecular mechanism of Presenilin-1 (PS1) linked Alzheimer's Disease pathology
    Oksana Berezovska; Fiscal Year: 2010
    ..More generally, the assay of monitoring PS1 conformation and y-secretase -substrate proximity will help to help develop methodologies that may prove useful in understanding disease-related protein conformation changes. ..
  43. POMC Processing and Beta-Endorphine-Related Opioid Peptides
    Vivian Y H Hook; Fiscal Year: 2010
    ..New findings from this project will enhance our knowledge of the complexity of biosynthetic mechanisms for endogenous opioid and neuropeptide systems. ..
  44. Serpin Protease Inhibitors & Opioid Neuropeptides
    Vivian Hook; Fiscal Year: 2006
    ..Serpin regulation of opioid peptides that mediate analgesia and stress may lead to development of new therapeutic approaches in pain and neurologic disease. ..
  45. Transgenic Model for Cerebral Amyloid Angiopathy
    William Van Nostrand; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  46. Molecular & Behavioral Effects of Low Level Mn Exposure
    TOMAS GUILARTE; Fiscal Year: 2008
    ..The knowledge gained will help set future public health policies and guidelines to limit Mn exposures in occupational settings and to the general population. ..
  47. Interaction of ABeta & the alpha7 AChR in mouse AD model
    JOANNA JANKOWSKY; Fiscal Year: 2008
    ..abstract_text> ..
  48. Therapeutic Effects of Intranasal Insulin in AD
    Suzanne Craft; Fiscal Year: 2008
    ..We will also obtain critical information about the overarching theory that lowered CNS insulin and peripheral insulin resistance contribute to AD pathophysiology. [unreadable] [unreadable]..
  49. EPIDEMIOLOGY OF DEMENTIA IN AN URBAN COMMUNITY
    Richard Mayeux; Fiscal Year: 2008
    ..The overall theme of this fourth renewal application is to identify reliable and valid antecedent biomarkers of AD and MCI and to extend these and other clinical parameters to the measurement of disease progression. ..
  50. AntiRetroviral Activities of NEBRI
    Tsuneya Ikezu; Fiscal Year: 2003
    ..The potential of NEBR1 to effect viral-host cell interactions is realistic, novel and contains therapeutic implications. ..
  51. CELLULAR FUNCTIONS OF ALZHEIMER'S DISEASE PROTEINS
    NAZNEEN DEWJI; Fiscal Year: 2004
    ....
  52. Regulation of calcium signaling pathways by presenilins
    Frank LaFerla; Fiscal Year: 2005
    ..Lastly, by manipulating calcium signaling and determining its effects on AB production, aim 5 will address whether the effects of presenilin mutations on calcium signaling are necessary and/or sufficient to increase Ab formation. ..
  53. Modulating IBM pathology in transgenic mice
    Frank LaFerla; Fiscal Year: 2005
    ....
  54. Neonatal exposure & neurodegeneration of the aged brain
    Nasser Zawia; Fiscal Year: 2006
    ..We would like to test this hypothesis by examining the effect of Pb exposure on DNA-methylation and determine whether these actions selectively impact genes rich in GC box elements such as APP and BACE. ..
  55. APP Mediated Mitochondrial Injury in Aging Neurons
    ANAND HINDUPUR; Fiscal Year: 2007
    ..abstract_text> ..
  56. Cellular signaling and Trafficking of APP Family Members
    LUCIANO D ADAMIO; Fiscal Year: 2007
    ..These studies may clarify the biological role of APP family members and have important practical applications in the development of new compounds for the cure and or prevention of Alzheimer's disease. ..
  57. Novel Animal Models of Familial British, Danish and Alzheimer's Dementia
    LUCIANO D ADAMIO; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  58. The role of Mnbk in Downs Syndrome brain development and aging
    Jerzy Wegiel; Fiscal Year: 2008
    ..This study will provide a foundation for identifying the mechanisms and morphological substrate of specific functional deficits, and should contribute to the improvement of diagnosis and treatment. ..
  59. GENETIC EPIDEMIOLOGY OF AGING IN A MULTIETHNIC COMMUNITY
    Richard Mayeux; Fiscal Year: 2002
    ....