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Human and murine ApoE markedly alters A beta metabolism before and after plaque formation in a mouse model of Alzheimer's disease.
Neurobiol Dis 2002; 9(3):305-18ND

Abstract

The epsilon4 allele of apolipoprotein E (apoE) is a risk factor for Alzheimer's disease (AD), perhaps through effects on amyloid-beta (Abeta) metabolism. Detailed analyses of various Abeta parameters in aging APP(V717F+/-) transgenic mice expressing mouse apoE, no apoE, or human apoE2, apoE3, or apoE4 demonstrate that apoE facilitates, but is not required for, Abeta fibril formation in vivo. Human apoE isoforms markedly delayed Abeta deposition relative to mouse apoE, with apoE2 (and apoE3 to a lesser extent) having a prolonged ability to prevent Abeta from converting into fibrillar forms. Isoform-specific effects of human apoE on Abeta levels and neuritic plaque formation mimicked that observed in AD (E4 > E3 > E2). Importantly, observation of an apoE-dependent decrease in percent soluble Abeta and enrichment of Abeta in membrane microdomains prior to Abeta deposition indicates that apoE influences Abeta metabolism early in the amyloidogenic process and provides a possible novel mechanism by which apoE affects AD pathogenesis.

Authors+Show Affiliations

Center for the Study of Nervous System Injury, Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. fagana@neuro.wustl.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11950276

Citation

Fagan, Anne M., et al. "Human and Murine ApoE Markedly Alters a Beta Metabolism Before and After Plaque Formation in a Mouse Model of Alzheimer's Disease." Neurobiology of Disease, vol. 9, no. 3, 2002, pp. 305-18.
Fagan AM, Watson M, Parsadanian M, et al. Human and murine ApoE markedly alters A beta metabolism before and after plaque formation in a mouse model of Alzheimer's disease. Neurobiol Dis. 2002;9(3):305-18.
Fagan, A. M., Watson, M., Parsadanian, M., Bales, K. R., Paul, S. M., & Holtzman, D. M. (2002). Human and murine ApoE markedly alters A beta metabolism before and after plaque formation in a mouse model of Alzheimer's disease. Neurobiology of Disease, 9(3), pp. 305-18.
Fagan AM, et al. Human and Murine ApoE Markedly Alters a Beta Metabolism Before and After Plaque Formation in a Mouse Model of Alzheimer's Disease. Neurobiol Dis. 2002;9(3):305-18. PubMed PMID: 11950276.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human and murine ApoE markedly alters A beta metabolism before and after plaque formation in a mouse model of Alzheimer's disease. AU - Fagan,Anne M, AU - Watson,Melanie, AU - Parsadanian,Maia, AU - Bales,Kelly R, AU - Paul,Steven M, AU - Holtzman,David M, PY - 2002/4/13/pubmed PY - 2002/8/14/medline PY - 2002/4/13/entrez SP - 305 EP - 18 JF - Neurobiology of disease JO - Neurobiol. Dis. VL - 9 IS - 3 N2 - The epsilon4 allele of apolipoprotein E (apoE) is a risk factor for Alzheimer's disease (AD), perhaps through effects on amyloid-beta (Abeta) metabolism. Detailed analyses of various Abeta parameters in aging APP(V717F+/-) transgenic mice expressing mouse apoE, no apoE, or human apoE2, apoE3, or apoE4 demonstrate that apoE facilitates, but is not required for, Abeta fibril formation in vivo. Human apoE isoforms markedly delayed Abeta deposition relative to mouse apoE, with apoE2 (and apoE3 to a lesser extent) having a prolonged ability to prevent Abeta from converting into fibrillar forms. Isoform-specific effects of human apoE on Abeta levels and neuritic plaque formation mimicked that observed in AD (E4 > E3 > E2). Importantly, observation of an apoE-dependent decrease in percent soluble Abeta and enrichment of Abeta in membrane microdomains prior to Abeta deposition indicates that apoE influences Abeta metabolism early in the amyloidogenic process and provides a possible novel mechanism by which apoE affects AD pathogenesis. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/11950276/Human_and_murine_ApoE_markedly_alters_A_beta_metabolism_before_and_after_plaque_formation_in_a_mouse_model_of_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969996102904833 DB - PRIME DP - Unbound Medicine ER -