Abeta

Summary

Gene Symbol: Abeta
Description: amyloid beta (A4) precursor protein
Alias: Abeta, Abpp, Adap, Cvap, E030013M08Rik, betaApp, amyloid beta A4 protein, alzheimer disease amyloid A4 protein homolog, amyloid precursor protein, amyloidogenic glycoprotein, appican, beta-amyloid precursor protein, protease nexin II
Species: mouse

Top Publications

  1. ncbi Age-related impairment of synaptic transmission but normal long-term potentiation in transgenic mice that overexpress the human APP695SWE mutant form of amyloid precursor protein
    S M Fitzjohn
    Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol, BS8 1TD, United Kingdom
    J Neurosci 21:4691-8. 2001
  2. 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
  3. 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
  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. 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
  6. 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
  7. pmc Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members
    Jochen Herms
    Zentrum für Neuropathologie und Prionforschung, Universitat Munchen, Munchen, Germany
    EMBO J 23:4106-15. 2004
  8. 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
  9. ncbi A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease
    C Janus
    Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Ontario, Canada
    Nature 408:979-82. 2000
  10. 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

Research Grants

Detail Information

Publications186 found, 100 shown here

  1. ncbi Age-related impairment of synaptic transmission but normal long-term potentiation in transgenic mice that overexpress the human APP695SWE mutant form of amyloid precursor protein
    S M Fitzjohn
    Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol, BS8 1TD, United Kingdom
    J Neurosci 21:4691-8. 2001
    ..mouse strain relevant to Alzheimer's disease (AD), overexpressing the 695 amino acid isoform of human amyloid precursor protein with K670N and M671L mutations (APP(695)SWE mice), which is associated with early-onset familial AD...
  2. 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...
  3. 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 ..
  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
    A locus segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21, close to the amyloid precursor protein (APP) gene...
  5. 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
    ..This evidence establishes a pathogenic sameness between familial Danish and Alzheimer's dementias...
  6. 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
    The amyloid precursor protein (APP) is a type I transmembrane protein of unknown physiological function...
  7. pmc Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members
    Jochen Herms
    Zentrum für Neuropathologie und Prionforschung, Universitat Munchen, Munchen, Germany
    EMBO J 23:4106-15. 2004
    The Alzheimer's disease beta-amyloid precursor protein (APP) is a member of a larger gene family that includes the amyloid precursor-like proteins, termed APLP1 and APLP2...
  8. 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
    It is well established that the proteolytic processing of the beta-amyloid precursor protein (APP) generates beta-amyloid (Abeta), which plays a central role in the pathogenesis of Alzheimer's disease (AD)...
  9. ncbi A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease
    C Janus
    Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Ontario, Canada
    Nature 408:979-82. 2000
    ..and extracellular deposition of amyloid-beta peptide (A beta), a proteolytic derivative of the beta-amyloid precursor protein (betaAPP), is central to the pathogenesis of Alzheimer's disease (reviewed in ref. 1)...
  10. 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
    Biochemical and genetic studies place the amyloid precursor protein (APP) at the center stage of Alzheimer's disease (AD) pathogenesis...
  11. 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
    ..tangles composed of tau and neuritic plaques comprising amyloid-beta peptides (Abeta) derived from amyloid precursor protein (APP), but their exact relationship remains elusive...
  12. 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
    Mutations in the amyloid precursor protein (APP) gene cause early-onset familial Alzheimer disease (AD) by affecting the formation of the amyloid beta (A beta) peptide, the major constituent of AD plaques...
  13. 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 several pedigrees of early onset familial Alzheimer's disease (FAD), point mutations in the beta-amyloid precursor protein (APP) gene are genetically linked to the disease...
  14. pmc High cholesterol-induced neuroinflammation and amyloid precursor protein processing correlate with loss of working memory in mice
    Lakshmi Thirumangalakudi
    Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Neurochem 106:475-85. 2008
    ..performance in rodent models of hypercholesterolemia in relation to neuroinflammatory changes and amyloid precursor protein (APP) processing, the two key parameters of Alzheimer's disease pathogenesis...
  15. pmc Beta amyloid-independent role of amyloid precursor protein in generation and maintenance of dendritic spines
    K J Lee
    Department of Pharmacology, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC 20057 1464, USA
    Neuroscience 169:344-56. 2010
    ..Abeta is generated by proteolysis of amyloid precursor protein (APP), a synaptic receptor whose physiological function remains unclear...
  16. doi Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model
    Chiho Hirata-Fukae
    Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA
    Brain Res 1216:92-103. 2008
    ..Though transgenic mouse models of AD develop AD-related amyloid beta (Abeta) and/or tau pathology, gender differences have not been well documented in these models...
  17. 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
    ..Analyses of mice harboring the MoPrP.Xho construct with cDNA genes encoding the amyloid precursor protein (APP) and human presenilin 1 demonstrated that this vector provides relatively high levels of transgene-..
  18. pmc Rodent A beta modulates the solubility and distribution of amyloid deposits in transgenic mice
    Joanna L Jankowsky
    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    J Biol Chem 282:22707-20. 2007
    The amino acid sequence of amyloid precursor protein (APP) is highly conserved, and age-related A beta aggregates have been described in a variety of vertebrate animals, with the notable exception of mice and rats...
  19. ncbi Amyloid precursor protein knockout mice show age-dependent deficits in passive avoidance learning
    Yann Senechal
    Neuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Lichtstrasse 35, CH 4056 Basel, Switzerland
    Behav Brain Res 186:126-32. 2008
    b>Amyloid precursor protein (APP) is involved in the pathogenesis of Alzheimer's disease (AD), but its role in cognition has been relatively little studied...
  20. pmc Expression in brain of amyloid precursor protein mutated in the alpha-secretase site causes disturbed behavior, neuronal degeneration and premature death in transgenic mice
    D Moechars
    Experimental Genetics Group, Center for Human Genetics, Leuven, Belgium
    EMBO J 15:1265-74. 1996
    A double mutation in the alpha-secretase site in the betaA4 region of mouse amyloid precursor protein (APP) reduced its secretion from COS cells, polarized MDCK cells and rat primary neurons...
  21. pmc LRAD3, a novel low-density lipoprotein receptor family member that modulates amyloid precursor protein trafficking
    Sripriya Ranganathan
    Center for Vascular and Inflammatory Diseases and the Departments of Surgery and Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    J Neurosci 31:10836-46. 2011
    ..In the mouse hippocampal-derived cell line HT22, LRAD3 partially colocalizes with amyloid precursor protein (APP) and interacts with APP as revealed by coimmunoprecipitation experiments...
  22. pmc α-Secretase-derived fragment of cellular prion, N1, protects against monomeric and oligomeric amyloid β (Aβ)-associated cell death
    Marie Victoire Guillot-Sestier
    Institut de Pharmacologie Moleculaire et Cellulaire, UMR6097 CNRS Université de Nice Sophia Antipolis UNSA, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France
    J Biol Chem 287:5021-32. 2012
    In physiological conditions, both β-amyloid precursor protein (βAPP) and cellular prion (PrP(c)) undergo similar disintegrin-mediated α-secretase cleavage yielding N-terminal secreted products referred to as soluble amyloid precursor ..
  23. pmc Novel GαS-protein signaling associated with membrane-tethered amyloid precursor protein intracellular domain
    Carole Deyts
    Department of Neurobiology, Neurology, and Pathology, The University of Chicago, Chicago, Illinois 60637, USA
    J Neurosci 32:1714-29. 2012
    ..including a role as a cell surface receptor, have been ascribed to Alzheimer's disease-associated amyloid precursor protein (APP). However, detailed analysis of intracellular signaling mediated by APP in neurons has been lacking...
  24. ncbi Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes
    L Holcomb
    Department of Pharmacology, University of South Florida, Tampa 33612, USA
    Nat Med 4:97-100. 1998
    Genetic causes of Alzheimer's disease (AD) include mutations in the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2) genes...
  25. pmc Altered temporal patterns of anxiety in aged and amyloid precursor protein (APP) transgenic mice
    Tracy A Bedrosian
    Department of Neuroscience, Institute for Behavioral Medicine Research, Ohio State University Medical Center, Columbus, OH 43210, USA
    Proc Natl Acad Sci U S A 108:11686-91. 2011
    ..In the present study, we explored the diurnal pattern of anxiety-like behavior in aged and amyloid precursor protein (APP) transgenic mice...
  26. ncbi A mouse model for Down syndrome exhibits learning and behaviour deficits
    R H Reeves
    Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nat Genet 11:177-84. 1995
    ..The corresponding dosage imbalance for the human homologues of these genes may contribute to cognitive deficits in DS...
  27. 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.
  28. ncbi Fibrillar beta-amyloid-stimulated intracellular signaling cascades require Vav for induction of respiratory burst and phagocytosis in monocytes and microglia
    Brandy Wilkinson
    Alzheimer Research Laboratory, Department of Neuroscience, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Biol Chem 281:20842-50. 2006
    ..Co-immunoprecipitation studies demonstrate an Abeta-dependent association between Vav and both Lyn and Syk kinases...
  29. 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
    ..amyloid plaques are composed of amyloid beta-peptide (A beta), a 40-42-amino-acid fragment of the beta-amyloid precursor protein (APP)...
  30. ncbi Hypersensitivity to seizures in beta-amyloid precursor protein deficient mice
    J P Steinbach
    Institute of Neuropathology, University Hospital, Zurich, Switzerland
    Cell Death Differ 5:858-66. 1998
    Secreted forms of the beta-amyloid precursor protein (beta-APP) have neuroprotective properties in vitro and may be involved in the containment of neuronal excitation...
  31. ncbi Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain
    D Moechars
    Experimental Genetics Group, Center for Human Genetics, Flemish Institute for Biotechnology, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    J Biol Chem 274:6483-92. 1999
    Transgenic mice overexpressing different forms of amyloid precursor protein (APP), i.e...
  32. pmc Abeta-induced inflammatory processes in microglia cells of APP23 transgenic mice
    K D Bornemann
    Novartis Pharma AG, Nervous System Research, and the Institute of Pathology, University of Basel, Basel, Switzerland
    Am J Pathol 158:63-73. 2001
    ..We have used APP23 transgenic mice overexpressing human amyloid precursor protein with the Swedish mutation to characterize this microglia response to amyloid deposits in aged mice...
  33. pmc Decreased brain-derived neurotrophic factor depends on amyloid aggregation state in transgenic mouse models of Alzheimer's disease
    Shiyong Peng
    Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
    J Neurosci 29:9321-9. 2009
    ..These findings also suggest that the effect of A beta on decreased BDNF expression is specific to the aggregation state of A beta and is dependent on large oligomers...
  34. doi Gamma-secretase inhibition reduces spine density in vivo via an amyloid precursor protein-dependent pathway
    Tobias Bittner
    Center of Neuropathology and Prion Research, Ludwig Maximilians Universitat, Munich, Germany
    J Neurosci 29:10405-9. 2009
    ..In mice deficient for the amyloid precursor protein (APP), both GSIs had no effect on dendritic spine density, demonstrating that gamma-secretase inhibition ..
  35. pmc Presynaptic and postsynaptic interaction of the amyloid precursor protein promotes peripheral and central synaptogenesis
    Zilai Wang
    Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, USA
    J Neurosci 29:10788-801. 2009
    A critical role of the amyloid precursor protein (APP) in Alzheimer's disease (AD) pathogenesis has been well established. However, the physiological function of APP remains elusive and much debated...
  36. pmc Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid
    M E Calhoun
    Department of Neuropathology, Institute for Pathology, University of Basel, CH 4003 Basel, Switzerland
    Proc Natl Acad Sci U S A 96:14088-93. 1999
    Transgenic mice that overexpress mutant human amyloid precursor protein (APP) exhibit one hallmark of Alzheimer's disease pathology, namely the extracellular deposition of amyloid plaques...
  37. pmc Tyr(682) in the intracellular domain of APP regulates amyloidogenic APP processing in vivo
    Alessia P M Barbagallo
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America
    PLoS ONE 5:e15503. 2010
    ..For example, normal Aβ generation and secretion are dependent upon Tyr(682) in vitro. However, physiological functions of Tyr(682) are unknown...
  38. 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
    ..enzyme 1 (BACE1), presenilins (PS), and other proteins of the gamma-secretase complex liberate beta-amyloid (Abeta) peptides from larger integral membrane proteins, termed beta-amyloid precursor proteins (APPs)...
  39. ncbi Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses
    Claudia G Almeida
    Department of Neurology and Neuroscience, Laboratory of Alzheimer s Disease Neurobiology, Weill Medical College of Cornell University, 525 E 68th Street, NY 10021, USA
    Neurobiol Dis 20:187-98. 2005
    ..viewed as an early manifestation of Alzheimer's disease (AD), but the cellular mechanism by which beta-amyloid (Abeta) may affect synapses remains unclear...
  40. 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...
  41. pmc Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle
    Jae Eun Kang
    Department of Neurology, Washington University, St Louis, MO 63110, USA
    Science 326:1005-7. 2009
    ..significantly increased, and a dual orexin receptor antagonist decreased, Abeta plaque formation in amyloid precursor protein transgenic mice...
  42. pmc The intracellular threonine of amyloid precursor protein that is essential for docking of Pin1 is dispensable for developmental function
    Alessia P M Barbagallo
    Department of Microbiology and Immunology, Einstein College of Medicine, Bronx, New York, United States of America
    PLoS ONE 6:e18006. 2011
    ..Thr residue at amino acid 668 of the APP intracellular domain (AID) is highly conserved. When phosphorylated, this residue generates a binding site for Pin1. The interaction of APP with Pin1 has been involved in AD pathogenesis...
  43. ncbi Role of APP phosphorylation in FE65-dependent gene transactivation mediated by AICD
    Tadashi Nakaya
    Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita ku, Sapporo 060 0812, Japan
    Genes Cells 11:633-45. 2006
    ..Therefore, phosphorylation of APP but not AICD modulates FE65-dependent gene transactivation mediated by AICD through the regulation of FE65 intracellular localization...
  44. doi APP involvement in retinogenesis of mice
    Virginie Dinet
    Centre de Recherche des Cordeliers, Universite Pierre et Marie Curie, Paris 6, INSERM, 15 rue de l Ecole de Medecine, Paris, France
    Acta Neuropathol 121:351-63. 2011
    Very few studies have examined expression and function of amyloid precursor protein (APP) in the retina. We showed that APP mRNA and protein are expressed according to the different waves of retinal differentiation...
  45. pmc Mitochondrial dysfunction in skeletal muscle of amyloid precursor protein-overexpressing mice
    Simona Boncompagni
    CeSI Centro Scienze dell Invecchiamento and DNI Department of Neuroscience and Imaging, University Gabriele D Annunzio, I 66100 Chieti, Italy
    J Biol Chem 287:20534-44. 2012
    ..the most common muscle disorder in the elderly, is partly characterized by abnormal expression of amyloid precursor protein (APP) and intracellular accumulation of its proteolytic fragments collectively known as β-amyloid...
  46. pmc Tyr682 in the Aβ-precursor protein intracellular domain regulates synaptic connectivity, cholinergic function, and cognitive performance
    Carmela Matrone
    CNR National Research Council, Cell Biology and Neurobiology Institute, Rome, 00143, Italy
    Aging Cell 11:1084-93. 2012
    ..The profound deficits caused by the Y682 mutation underscore the biological importance of APP and indicate that APP(YG/YG) are a valuable mouse model to study APP functions in physiological and pathological processes...
  47. ncbi Neurobehavioral development, adult openfield exploration and swimming navigation learning in mice with a modified beta-amyloid precursor protein gene
    P Tremml
    Institute of Anatomy, University of Zurich Irchel, Zurich, Switzerland
    Behav Brain Res 95:65-76. 1998
    The processing of beta-amyloid precursor protein (betaAPP) and its metabolites plays an important role in the pathogenesis of Alzheimer's disease (AD) and Down's syndrome...
  48. 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...
  49. pmc Coordinated transport of phosphorylated amyloid-beta precursor protein and c-Jun NH2-terminal kinase-interacting protein-1
    Zoia Muresan
    Department of Physiology and Biophysics, Case School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
    J Cell Biol 171:615-25. 2005
    ..These results indicate that the phosphorylation of APP regulates the formation of a pAPP-JIP-1 complex that accumulates in neurites independent of nonphosphorylated APP...
  50. pmc Regulation of amyloid beta-protein precursor by phosphorylation and protein interactions
    Toshiharu Suzuki
    Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita ku, Sapporo 060 0812, Japan
    J Biol Chem 283:29633-7. 2008
    ..Recent findings regarding the regulation of APP processing contribute to the development of novel drugs and/or therapies for Alzheimer disease...
  51. doi Generation of conditional null alleles for APP and APLP2
    Jan Philipp Mallm
    Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany
    Genesis 48:200-6. 2010
    Proteolytical cleavage of the beta-amyloid precursor protein (APP) generates beta-amyloid, which is deposited in the brains of patients suffering from Alzheimer's disease (AD)...
  52. ncbi Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins
    K K Hsiao
    Department of Neurology, University of Minnesota, Minneapolis 55455, USA
    Neuron 15:1203-18. 1995
    Transgenic FVB/N mice overexpressing human (Hu) or mouse (Mo) Alzheimer amyloid precursor protein (APP695) die early and develop a CNS disorder that includes neophobia and impaired spatial alternation, with diminished glucose utilization ..
  53. ncbi Alzheimer's disease: genetic studies and transgenic models
    D L Price
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2196, USA
    Annu Rev Genet 32:461-93. 1998
    ..some of the genes/proteins that are causative or risk factors for this disease, including those encoding amyloid precursor protein, presenilin 1 and 2, and apolipoprotein E...
  54. pmc Genetic background changes the pattern of forebrain commissure defects in transgenic mice underexpressing the beta-amyloid-precursor protein
    F Magara
    Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Proc Natl Acad Sci U S A 96:4656-61. 1999
    We previously have reported corpus callosum defects in transgenic mice expressing the beta-amyloid precursor protein (betaAPP) with a deletion of exon 2 and at only 5% of normal levels...
  55. ncbi Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein
    G R Seabrook
    Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK
    Neuropharmacology 38:349-59. 1999
    Abnormal processing of amyloid precursor protein (APP), in particular the generation of beta-amyloid (Abeta) peptides, has been implicated in the pathogenesis of Alzheimer's disease...
  56. pmc Presenilin 2 deficiency causes a mild pulmonary phenotype and no changes in amyloid precursor protein processing but enhances the embryonic lethal phenotype of presenilin 1 deficiency
    A Herreman
    Neuronal Cell Biology Laboratory, K U Leuven and Flanders Institute for Biotechnology, 3000 Leuven, Belgium
    Proc Natl Acad Sci U S A 96:11872-7. 1999
    ..Absence of PS2 does not detectably alter processing of amyloid precursor protein and has little or no effect on physiologically important apoptotic processes, indicating that Alzheimer'..
  57. ncbi Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model
    L M Refolo
    Nathan S Kline Institute for Dementia Research, Orangeburg, New York, USA
    Neurobiol Dis 7:321-31. 2000
    ..levels of sAPPalpha and increased levels of C-terminal fragments (beta-CTFs), suggesting alterations in amyloid precursor protein processing in response to hypercholesterolemia...
  58. doi Embryonic stem cell-derived neurons as a cellular system to study gene function: lack of amyloid precursor proteins APP and APLP2 leads to defective synaptic transmission
    Katrin Schrenk-Siemens
    Neurodegeneration Department, Neuroscience Research, Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland
    Stem Cells 26:2153-63. 2008
    ..This is of particular interest when mutations lead to lethal in vivo phenotypes. Although the amyloid precursor protein (APP) and its proteolysis are regarded as key elements of the pathology of Alzheimer's disease, the ..
  59. 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
    ..the Notch intracellular domain (NICD), and is reminiscent of gamma-secretase-mediated cleavage of beta-amyloid precursor protein (APP), a critical event in the pathogenesis of Alzheimer's disease...
  60. ncbi c-Jun N-terminal kinase (JNK)-interacting protein-1b/islet-brain-1 scaffolds Alzheimer's amyloid precursor protein with JNK
    S Matsuda
    Department of Pharmacology and Neurosciences, Keio University School of Medicine, Shinjuku ku, Tokyo 160 8582, Japan
    J Neurosci 21:6597-607. 2001
    Using a yeast two-hybrid method, we searched for amyloid precursor protein (APP)-interacting molecules by screening mouse and human brain libraries...
  61. ncbi Microglial activation and beta -amyloid deposit reduction caused by a nitric oxide-releasing nonsteroidal anti-inflammatory drug in amyloid precursor protein plus presenilin-1 transgenic mice
    Paul T Jantzen
    Department of Pharmacology, Alzheimer s Research Laboratory, University of South Florida, Tampa, Florida 33612, USA
    J Neurosci 22:2246-54. 2002
    ..dramatically reduced both beta-amyloid (Abeta) loads and Congo red staining in doubly transgenic (Tg) amyloid precursor protein plus presenilin-1 mice when administered at 375 ppm in diet between 7 and 12 months of age...
  62. ncbi Presenilin redistribution associated with aberrant cholesterol transport enhances beta-amyloid production in vivo
    Mark Burns
    Center for Dementia Research, Nathan S Kline Institute, Orangeburg, New York 10962, USA
    J Neurosci 23:5645-9. 2003
    ..We have examined the impact of aberrant intracellular cholesterol transport on the processing of the amyloid precursor protein (APP) in a mouse model of Niemann-Pick type C (NPC) disease...
  63. ncbi Growth factor receptor-bound protein 2 interaction with the tyrosine-phosphorylated tail of amyloid beta precursor protein is mediated by its Src homology 2 domain
    Dawang Zhou
    Albert Einstein College of Medicine, Department of Microbiology and Immunology, Bronx, New York 10461, USA
    J Biol Chem 279:25374-80. 2004
    ....
  64. ncbi Cognitive correlates of Abeta deposition in male and female mice bearing amyloid precursor protein and presenilin-1 mutant transgenes
    David R Howlett
    Neurology and GI CEDD, GlaxoSmithKline Research and Development Limited, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK
    Brain Res 1017:130-6. 2004
    Several transgenic mouse models of Alzheimer's disease (AD) have been developed that exhibit beta-amyloid (Abeta) neuropathology and behavioural deficits...
  65. pmc Neuronal membrane cholesterol loss enhances amyloid peptide generation
    Jose Abad-Rodriguez
    Cavalieri Ottolenghi Scientific Institute, Universita degli Studi di Torino, Orbassano, Italy
    J Cell Biol 167:953-60. 2004
    ....
  66. pmc Transforming growth factor beta2 is a neuronal death-inducing ligand for amyloid-beta precursor protein
    Yuichi Hashimoto
    Department of Pharmacology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku ku, Tokyo 160 8582, Japan
    Mol Cell Biol 25:9304-17. 2005
    ....
  67. ncbi Progressive neuronal loss and behavioral impairments of transgenic C57BL/6 inbred mice expressing the carboxy terminus of amyloid precursor protein
    Kang Woo Lee
    Department of Neuroscience, Neuroscience Research Center and Medical Research Institute, Ewha Womans University School of Medicine, 911 1 Mok 6 dong, YangChun Gu, Seoul 158 710, South Korea
    Neurobiol Dis 22:10-24. 2006
    The beta-secretase cleaved Abeta-bearing carboxy-terminal fragments (betaCTFs) of amyloid precursor protein (APP) in neural cells have been suggested to be cytotoxic...
  68. ncbi Apolipoprotein E and low density lipoprotein receptor-related protein facilitate intraneuronal Abeta42 accumulation in amyloid model mice
    Celina V Zerbinatti
    Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 281:36180-6. 2006
    ..protein (LRP) is highly expressed in the brain and has been shown to alter the metabolism of amyloid precursor protein and amyloid-beta peptide (Abeta) in vitro...
  69. pmc Modulation of gene expression and cytoskeletal dynamics by the amyloid precursor protein intracellular domain (AICD)
    Thorsten Müller
    Institute of Pathology and Neuropathology, University Hospital Essen, D 45122 Essen, Germany
    Mol Biol Cell 18:201-10. 2007
    Amyloidogenic processing of the amyloid precursor protein (APP) results in the generation of beta-amyloid, the main constituent of Alzheimer plaques, and the APP intracellular domain (AICD)...
  70. pmc Physiological mouse brain Abeta levels are not related to the phosphorylation state of threonine-668 of Alzheimer's APP
    Yoshitake Sano
    RIKEN, Brain Science Institute, Behavioral Genetics, Wako, Japan
    PLoS ONE 1:e51. 2006
    ..at positions 40 and 42 (Abeta40, Abeta42) are generated by the proteolytic processing of the Alzheimer's amyloid precursor protein (APP)...
  71. pmc Neuroanatomical localization and quantification of amyloid precursor protein mRNA by in situ hybridization in the brains of normal, aneuploid, and lesioned mice
    C Bendotti
    Johns Hopkins University School of Medicine, Baltimore, MD 21205
    Proc Natl Acad Sci U S A 85:3628-32. 1988
    b>Amyloid precursor protein mRNA was localized in frozen sections from normal and experimentally lesioned adult mouse brain and from normal and aneuploid fetal mouse brain by in situ hybridization with a 35S-labeled mouse cDNA probe...
  72. pmc Inflammatory processes induce beta-amyloid precursor protein changes in mouse brain
    B Brugg
    Universite P and M Curie, Institut des Neurosciences Unité de Recherche Associée 1488, Centre National de la Recherche Scientifique, Paris, France
    Proc Natl Acad Sci U S A 92:3032-5. 1995
    ..a combination of genetic predisposition and environmental factors may contribute to changes in beta-amyloid precursor protein (APP) expression, beta-amyloid peptide deposition, and neuronal loss...
  73. ncbi Behavioral and anatomical deficits in mice homozygous for a modified beta-amyloid precursor protein gene
    U Muller
    Institut für Molekularbiologie I, Universitat Zurich, Switzerland
    Cell 79:755-65. 1994
    The beta-amyloid precursor protein (beta APP) gene of the mouse was disrupted by inserting into exon 2 a cassette containing a neomycin resistance gene and a putative transcription termination sequence...
  74. ncbi Peptides containing the RERMS sequence of amyloid beta/A4 protein precursor bind cell surface and promote neurite extension
    L W Jin
    Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla 92093 0624
    J Neurosci 14:5461-70. 1994
    ..These data indicate that sAPP induces neurite extension through cell-surface binding and that the domain containing the RERMS sequence (APP 328-332) represents the active site responsible for this function...
  75. pmc Generation of mice with a 200-kb amyloid precursor protein gene deletion by Cre recombinase-mediated site-specific recombination in embryonic stem cells
    Z W Li
    Institut für Molekularbiologie der Universität Zürich, Switzerland
    Proc Natl Acad Sci U S A 93:6158-62. 1996
    ..Because we could not obtain a deletion of about 200 kb in the mouse amyloid precursor protein gene by the classical technique, we employed strategies involving the insertion of loxP sites upstream ..
  76. ncbi The beta-amyloid precursor protein of Alzheimer's disease enhances neuron viability and modulates neuronal polarity
    R G Perez
    Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 17:9407-14. 1997
    beta-Amyloid precursor protein (betaPP) can reside at neuron and glial cell surfaces or undergo proteolytic processing into secreted fragments. Although betaPP has been studied extensively, its precise physiological role is unknown...
  77. 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
    b>Amyloid precursor protein (APP) is a member of a larger gene family including amyloid precursor-like proteins (APLP), APLP2 and APLP1. To examine the function of APLP2 in vivo, we generated APLP2 knockout (KO) mice...
  78. ncbi Age-related cognitive deficits, impaired long-term potentiation and reduction in synaptic marker density in mice lacking the beta-amyloid precursor protein
    G R Dawson
    Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK
    Neuroscience 90:1-13. 1999
    Mutations in the beta-amyloid precursor protein are strongly associated with some cases of familial Alzheimer's disease...
  79. ncbi No hippocampal neuron or synaptic bouton loss in learning-impaired aged beta-amyloid precursor protein-null mice
    A L Phinney
    Neuropathology Laboratory, Institute of Pathology, University of Basel, Switzerland
    Neuroscience 90:1207-16. 1999
    Aged beta-amyloid precursor protein-null mice were used to investigate the relationship between beta-amyloid precursor protein, hippocampal neuron and synaptic bouton number, and cognitive function...
  80. ncbi Intracellular accumulation of detergent-soluble amyloidogenic A beta fragment of Alzheimer's disease precursor protein in the hippocampus of aged transgenic mice
    Q X Li
    Department of Pathology, University of Melbourne, and Mental Health Research Institute of Victoria, Parkville, Australia
    J Neurochem 72:2479-87. 1999
    ..in vivo, we created two transgenic (Tg) mouse lines expressing the C-terminal 100 amino acids of human amyloid precursor protein (APP): Tg C100.V717F and Tg C100.WT...
  81. ncbi Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse
    D Schenk
    Elan Pharmaceuticals, South San Francisco, California 94080, USA
    Nature 400:173-7. 1999
    ..Familial forms of the disease have been linked to mutations in the amyloid precursor protein (APP) and the presenilin genes...
  82. ncbi Amyloid production and deposition in mutant amyloid precursor protein and presenilin-1 yeast artificial chromosome transgenic mice
    B T Lamb
    Department of Genetics, Case Western Reserve University, Cleveland, Ohio 44106 4955, USA
    Nat Neurosci 2:695-7. 1999
  83. ncbi Disabled-1 binds to the cytoplasmic domain of amyloid precursor-like protein 1
    R Homayouni
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Neurosci 19:7507-15. 1999
    ..Indeed, we found that Dab1 also interacts with amyloid precursor protein (APP) and APLP2 in biochemical association experiments...
  84. 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
    ..were generated encoding wild-type hAPP or hAPP carrying mutations that alter the production of amyloidogenic Abeta peptides. The platelet-derived growth factor beta chain promoter was used to express these constructs in neurons...
  85. ncbi Developmental regulation of amyloid precursor protein at the neuromuscular junction in mouse skeletal muscle
    M Akaaboune
    INSERM Unité 523, Institut de Myologie, Paris, France
    Mol Cell Neurosci 15:355-67. 2000
    b>Amyloid precursor protein (APP), associated with Alzheimer's disease plaques, is known to be present in synapses of the brain and in the adult neuromuscular junction (NMJ)...
  86. 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
    The amyloid precursor protein (APP) involved in Alzheimer's disease is a member of a larger gene family including amyloid precursor-like proteins APLP1 and APLP2...
  87. pmc beta-site APP cleaving enzyme mRNA expression in APP transgenic mice: anatomical overlap with transgene expression and static levels with aging
    M C Irizarry
    Alzheimer Disease Research Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Am J Pathol 158:173-7. 2001
    The principal enzyme responsible for the beta-site cleavage of amyloid precursor protein (APP) in the brain is a membrane-bound aspartyl protease beta-site APP cleaving enzyme (BACE)...
  88. ncbi Comparative analysis of amyloid-beta chemical structure and amyloid plaque morphology of transgenic mouse and Alzheimer's disease brains
    Y M Kuo
    Longtine Center for Molecular Biology and Genetics and the Civin Laboratory of Neuropathology, Sun Health Research Institute, Sun City, Arizona 85351, USA
    J Biol Chem 276:12991-8. 2001
    We have undertaken an integrated chemical and morphological comparison of the amyloid-beta (Abeta) molecules and the amyloid plaques present in the brains of APP23 transgenic (tg) mice and human Alzheimer's disease (AD) patients...
  89. ncbi Spontaneous hemorrhagic stroke in a mouse model of cerebral amyloid angiopathy
    D T Winkler
    Department of Neuropathology, Institute of Pathology, University of Basel, CH 4003 Basel, Switzerland
    J Neurosci 21:1619-27. 2001
    ..We now report that CAA in an amyloid precursor protein transgenic mouse model (APP23 mice) leads to a loss of vascular smooth muscle cells, aneurysmal ..
  90. 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
    ..TgCRND8 mice encode a double mutant form of amyloid precursor protein 695 (KM670/671NL+V717F) under the control of the PrP gene promoter...
  91. ncbi Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice
    R A Cherny
    Department of Pathology, The University of Melbourne and, The Mental Health Research Institute of Victoria, Australia
    Neuron 30:665-76. 2001
    Inhibition of neocortical beta-amyloid (Abeta) accumulation may be essential in an effective therapeutic intervention for Alzheimer's disease (AD)...
  92. ncbi Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc
    Philip E Tarr
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 277:16798-804. 2002
    beta-Amyloid precursor protein (APP) is a widely expressed transmembrane protein of unknown function that is involved in the pathogenesis of Alzheimer's disease...
  93. ncbi Apolipoprotein E4 potentiates amyloid beta peptide-induced lysosomal leakage and apoptosis in neuronal cells
    Zhong Sheng Ji
    Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94141 9100, USA
    J Biol Chem 277:21821-8. 2002
    ....
  94. ncbi FAD mutant PS-1 gene-targeted mice: increased A beta 42 and A beta deposition without APP overproduction
    Dorothy G Flood
    Department of Neurobiology, Cephalon, Inc, West Chester, PA 19380, USA
    Neurobiol Aging 23:335-48. 2002
    ..When crossed into Tg(HuAPP695.K670N/M671L)2576 mice, the PS-1(P264L) mutation accelerated the onset of amyloid (Abeta) deposition in a gene-dosage dependent manner...
  95. pmc The gamma-secretase-generated intracellular domain of beta-amyloid precursor protein binds Numb and inhibits Notch signaling
    Roberta Roncarati
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 99:7102-7. 2002
    The beta-amyloid precursor protein (APP) and the Notch receptor undergo intramembranous proteolysis by the Presenilin-dependent gamma-secretase...
  96. ncbi Plaque-associated disruption of CSF and plasma amyloid-beta (Abeta) equilibrium in a mouse model of Alzheimer's disease
    Ronald B DeMattos
    Center for the Study of Nervous System Injury, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurochem 81:229-36. 2002
    To better understand amyloid-beta (Abeta) metabolism in vivo, we assessed the concentration of Abeta in the CSF and plasma of APP(V717F) (PDAPP) transgenic mice, a model that develops age-dependent Alzheimer's disease (AD)-like pathology...
  97. ncbi Capacitive calcium entry is directly attenuated by mutant presenilin-1, independent of the expression of the amyloid precursor protein
    Jochen Herms
    Department of Neuropathology, Ludwig Maximilians Universitat, 81377 Munich, Germany
    J Biol Chem 278:2484-9. 2003
    ..mice to demonstrate that mutant PS1 attenuated CCE directly, independent of the expression of the amyloid precursor protein (APP)...
  98. ncbi Early-onset and robust cerebral microvascular accumulation of amyloid beta-protein in transgenic mice expressing low levels of a vasculotropic Dutch/Iowa mutant form of amyloid beta-protein precursor
    Judianne Davis
    Department of Medicine, Health Sciences Center, Stony Brook University, Stony Brook, NY 11794 8153, USA
    J Biol Chem 279:20296-306. 2004
    Cerebrovascular deposition of amyloid beta-protein (Abeta) is a common pathological feature of Alzheimer's disease and related disorders...
  99. 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
    ....
  100. ncbi Presenilin-dependent transcriptional control of the Abeta-degrading enzyme neprilysin by intracellular domains of betaAPP and APLP
    Raphaelle Pardossi-Piquard
    Institut de Pharmacologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique, UMR6097 CNRS UNSA, Valbonne 06560, France
    Neuron 46:541-54. 2005
    ..role in Alzheimer's disease, is generated by presenilin-dependent gamma-secretase cleavage of beta-amyloid precursor protein (betaAPP). We report that the presenilins (PS1 and PS2) also regulate Abeta degradation...
  101. 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...

Research Grants40

  1. Biological Role of the FE65 Protein/APP Interactions
    Suzanne Guenette; Fiscal Year: 2009
    ..Processing of the amyloid precursor protein (APP) produces ABeta, the neuroprotective APPsa and the APP intracellular domain (AID/AICD) involved in ..
  2. A Beta Vaccination: Mechanisms and Therapautic Impact
    Lennart Mucke; Fiscal Year: 2005
    DESCRIPTION (provided by the applicant): The accumulation of beta-amyloid peptides (Abeta) in the brain plays a key role in Alzheimer's disease (AD)...
  3. Mouse model for neuroprotection
    Gopal Thinakaran; Fiscal Year: 2007
    ..Outcome of our investigation will be critical for the future development of STC2 based therapeutic strategy to prevent neuronal death. [unreadable] [unreadable]..
  4. BASIS OF SYNAPTIC PATHOLOGY IN ALZHEIMERS DISEASE
    Eliezer Masliah; Fiscal Year: 2001
    ..During the course of funding for this project the applicants have shown that abnormal functioning of amyloid precursor protein (APP) at the synaptic site might be involved in mechanisms of neurodegeneration in AD...
  5. Estrogen, NADPH Oxidase, and Neurotrauma
    Annadora Bruce Keller; Fiscal Year: 2006
    ..abstract_text> ..
  6. Defining presenilin-beta-catenin pathway in vivo
    Hui Zheng; Fiscal Year: 2006
    ..Presenilin is required for the processing of Notch and the b-amyloid precursor protein, molecules that play critical roles in development and AD pathogenesis respectively...
  7. Modulation of Alzheimer's Amyloidosis by Statins
    Anne M Cataldo; Fiscal Year: 2005
    Cerebral accumulation of Amyloid beta (Abeta) peptides is an early event in establishing of Alzheimer's disease (AD) pathology...
  8. Mechanisms of beta-Amyloid Precursor Protein Processing in the Brain
    NAZNEEN DEWJI; Fiscal Year: 2007
    ..membrane spanning and seven membrane spanning integral proteins, that one or more forms of the Beta-amyloid precursor protein (Beta-APP) and Presenilin 1 or 2 (PS-1 or 2) may normally be components of an intercellular juxtacrine ..
  9. Presenilins in tumorigenesis and neurodegeneration
    Hui Zheng; Fiscal Year: 2007
    ..They are indispensable for the proteolytic processing of a variety of substrates including Notch and the amyloid precursor protein (APP), molecules that play critical roles in cell fate determination and Alzheimer's disease (AD) ..
  10. Calpain Regulation of Amyloid-beta and Plaque Formation
    Paul Mathews; Fiscal Year: 2007
    ..shown that calpains, cytosolic, Ca++-activated neutral proteases, regulate ABeta formation from the amyloid precursor protein (APP) by altering the intracellular trafficking of this protein...
  11. PATHOGENIC MECHANISMS OF PRESENILIN MUTATION
    Robert Siman; Fiscal Year: 2007
    ..by applicant): Mutations in the genes encoding presenilins 1 and 2 (PS-1 and PS-2) and the beta-amyloid precursor protein (APP) are the leading cause of familial, early-onset Alzheimer's disease (FAD)...
  12. Beta-Amyloid Protofibrils Cause AD Neuronal Dysfunction
    Dean Hartley; Fiscal Year: 2006
    ..insidiously progressive pathophysiology is thought to be an age- related accumulation of amyloid beta-protein (Abeta) fibrils, ultimately observed as mature amyloid plaques at autopsy...
  13. Magnetic Resonance Imaging of Alzheimer's Amyloid Plaque
    JOSEPH PODUSLO; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  14. PRESENILIN DOMAINS AND RECONSTITUTION OF CATALYSIS
    Samuel Gandy; Fiscal Year: 2007
    ..the final step in the generation of the amyloid beta-peptide (AP) from the transmembrane Alzheimer amyloid precursor protein (APP)...
  15. Copper Complexing with Tetrathiomolybdate in a Murine Model of Alzheimers Disease
    Joseph Quinn; Fiscal Year: 2007
    ..These are the critical pieces of information for determining if TM should be evaluated in clinical trials for either the prevention or the treatment of Alzheimer's disease. [unreadable] [unreadable] [unreadable]..
  16. Mechanisms and use of antidiabetic agents in brain aging and Alzheimer's disease
    Olivier Thibault; Fiscal Year: 2008
    ..Furthermore, these studies will contribute to future drug discovery efforts to generate new TZD-derived or similar drugs for the treatment of AD. [unreadable] [unreadable] [unreadable]..
  17. Tat, NADPH oxidase, and HIV-dementia
    Annadora Bruce Keller; Fiscal Year: 2008
    ..Completion of these studies will result in a thorough understanding of the mechanisms of Tat-mediated neurotoxicity and could highlight a novel target for therapeutic intervention in HIVD. ..
  18. Functions of APP Family Members in Neuronal Development
    TRACY PEARSE; Fiscal Year: 2008
    Abeta is generated through beta- and gamma-secretase cleavage of amyloid precursor protein (APP)...
  19. METABOLISM OF THE VLDL RECEPTOR AND APOE RECEPTOR 2
    Joachim Herz; Fiscal Year: 2009
    ..This may provide novel targets for rational drug design and treatment of atherosclerosis as well as of AD, both disorders of increasing medical and socio-economic importance. ..
  20. Alzheimer disease biomarkers in lens
    Peter H Frederikse; Fiscal Year: 2010
    ..that fundamental neuron-specific cell biology processes that are focused on the Alzheimer beta-amyloid precursor protein (AbetaPP) are shared in the lens to a striking degree, and provided evidence that Abeta pathology is a ..
  21. THERAPEUTIC BENEFIT OF HYDROGEN PEROXIDE REMOVAL IN FALS
    JOSEPH PODUSLO; Fiscal Year: 2003
    ..This grant proposal, therefore, will further test whether this hypothesis-driven therapy is beneficial in the treatment of FALS transgenic mice, which will have direct implications for the treatment of both familial and sporadic ALS. ..
  22. BETA AMYLOID DERIVATION IN BRAIN IN ALZHEIMERS DISEASE
    NAZNEEN DEWJI; Fiscal Year: 2001
    Mutations in the genes for the beta-amyloid precursor protein (beta- APP), a type 1 single-membrane spanning integral protein, and the more recently identified closely homologous seven-membrane spanning integral proteins S182 and STM2, ..
  23. ROLE OF PRE FIBRILLAR AMYLOID IN ALZHEIMER'S DISEASE
    Dean Hartley; Fiscal Year: 2002
    ..underlying this progressive pathophysiology is thought to be an age-related accumulation of amyloid beta-protein (Abeta) fibrils, ultimately observed as mature amyloid plaques at autopsy...
  24. CAN MICROGLIAL CELLS PREVENT NEURONAL INJURY?
    Annadora Bruce Keller; Fiscal Year: 2002
    ..abstract_text> ..
  25. TRANSMITTER NEUROANATOMY IN ALZHEIMERS DISEASE
    Samuel Gandy; Fiscal Year: 2002
    ....
  26. 24-Capillary Reveal Mutation Discovery System
    George Carlson; Fiscal Year: 2003
    ..The Spectrumedix Reveal 2410 will not only accelerate current research at McLaughlin Research Institute, but help in recruiting new biomedical researchers in the field of neurogenetics. ..
  27. APO E Receptors and Modulation of Fast Axonal Transport
    Joachim Herz; Fiscal Year: 2006
    ....
  28. SYNAPTOGENESIS IN THE CEREBRAL CORTEX
    Chiye Aoki; Fiscal Year: 2003
    ..The knowledge gained from such a study is required in designing molecular remedies for deficits caused by sensory deprivation during early life. ..
  29. Cell-based screens for Alzheimer's disease therapeutics
    Paul Mathews; Fiscal Year: 2004
    ..ABeta is generated in two steps by the Beta- and gamma-proteolytic cleavages of the amyloid precursor protein (APP)...
  30. CELLULAR FUNCTIONS OF ALZHEIMER'S DISEASE PROTEINS
    NAZNEEN DEWJI; Fiscal Year: 2004
    DESCRIPTION (adapted from the application): Genetic evidence has implicated three proteins, the beta-amyloid precursor protein (beta-APP) and the two homologous presenilins (PS-1 and PS-2), in the etiology of Alzheimer's disease (AD)...
  31. OPIOID RECEPTORS ON T CELL SUBSETS
    Bonnie Miller; Fiscal Year: 2005
    ..Menk and dOR dependent modulation of viral clearance in a CD8+T cell and IFNg dependent murine model will be used to test the physiological relevance of in vitro findings in Aim 5. ..
  32. Biomarker for Alzheimer's Related Cognitive Deficits
    GRANT KRAFFT; Fiscal Year: 2005
    ..For testing of drugs that lower Abeta or ADDL levels, a quantitative ADDL diagnostic will be pivotal to establish that symptomatic efficacy parallels a ..
  33. CNS Stem Cells for Alzheimer's Disease Therapy
    George Carlson; Fiscal Year: 2005
    ..The objectives of this grant are to test human neural stern cells as candidate therapeutics for the treatment of Alzheimer's disease. ..
  34. Drug discovery of anti-ADDL therapeutics for Alzheimer's
    GRANT KRAFFT; Fiscal Year: 2005
    ..primary cause of Alzheimer's disease is the progressive accumulation of neurotpxic oligomeric assemblies of the Abeta 1-42 protein. These neurotoxic oligomeric species are known as ADDLs (Ab-derived diffusible ligands)...
  35. ABCA1: A Potential Therapeutic Target for AD
    Radosveta Koldamova; Fiscal Year: 2006
    ..and we demonstrated that ligands for LXRs increased ABCA1 expression in neuronal cells and reduced amyloid beta (ABeta) secretion...
  36. BABAA RECEPTORS IN AGING & ALZHEIMER'S DISEASE
    Samuel Gandy; Fiscal Year: 2002
    ....
  37. Chemically specified synaptogenesis in the visual cortex
    Chiye Aoki; Fiscal Year: 2004
    ..The knowledge gained from such a study is required in designing molecular remedies for deficits caused by sensory deprivation during early life. ..
  38. ALZHEIMER PATHOPHYSIOLOGY IN HUMAN CATARACT FORMATION
    PETER FREDERIKSE; Fiscal Year: 2002
    ..Beta-amyloid (ABeta) is cytotoxic to the lens by producing vacuoles and lens cell degeneration...
  39. Changes in cortical neurons and networks in mice overexpressing A beta
    Jack Waters; Fiscal Year: 2008
    ..These studies will provide critical insight into the cellular changes that occur in Alzheimer's disease and the resulting degeneration of neural networks. [unreadable] [unreadable] [unreadable]..
  40. Immunotherapy for Pancreatic Amylin Aggregates in Diabetes
    Einar Sigurdsson; Fiscal Year: 2008
    ..These studies could lead to novel treatments for type-2 diabetes. [unreadable] [unreadable] [unreadable]..