TY - JOUR
T1 - Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease
AU - Holtzman, David M.
AU - Bales, Kelly R.
AU - Tenkova, Tanya
AU - Fagan, Anne M.
AU - Parsadanian, Maia
AU - Sartorius, Leah J.
AU - Mackey, Brian
AU - Olney, John
AU - McKeel, Daniel
AU - Wozniak, David
AU - Paul, Steven M.
PY - 2000/3/14
Y1 - 2000/3/14
N2 - Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (ε4 > ε3) for Alzheimer's disease (AD). ApoE may affect AD pathogenesis by promoting deposition of the amyloid-β (Aβ) peptide and its conversion to a fibrillar form. To determine the effect of apoE on Aβ deposition and AD pathology, we compared APP(V717F) transgenic (TG) mice expressing mouse, human, or no apoE (apoE(-/-)). A severe, plaque-associated neuritic dystrophy developed in APP(V717F) TG mice expressing mouse or human apoE. Though significant levels of Aβ deposition also occurred in APP(V717F) TG, apoE(-/- ) mice, neuritic degeneration was virtually absent. Expression of apoE3 and apoE4 in APP(V717F) TG, apoE(-/-) mice resulted in fibrillar Aβ deposits and neuritic plaques by 15 months of age and substantially (>10-fold) more fibrillar deposits were observed in apoE4-expressing APP(V717F) TG mice. Our data demonstrate a critical and isoform-specific role for apoE in neuritic plaque formation, a pathological hallmark of AD.
AB - Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (ε4 > ε3) for Alzheimer's disease (AD). ApoE may affect AD pathogenesis by promoting deposition of the amyloid-β (Aβ) peptide and its conversion to a fibrillar form. To determine the effect of apoE on Aβ deposition and AD pathology, we compared APP(V717F) transgenic (TG) mice expressing mouse, human, or no apoE (apoE(-/-)). A severe, plaque-associated neuritic dystrophy developed in APP(V717F) TG mice expressing mouse or human apoE. Though significant levels of Aβ deposition also occurred in APP(V717F) TG, apoE(-/- ) mice, neuritic degeneration was virtually absent. Expression of apoE3 and apoE4 in APP(V717F) TG, apoE(-/-) mice resulted in fibrillar Aβ deposits and neuritic plaques by 15 months of age and substantially (>10-fold) more fibrillar deposits were observed in apoE4-expressing APP(V717F) TG mice. Our data demonstrate a critical and isoform-specific role for apoE in neuritic plaque formation, a pathological hallmark of AD.
UR - http://www.scopus.com/inward/record.url?scp=4243215848&partnerID=8YFLogxK
U2 - 10.1073/pnas.050004797
DO - 10.1073/pnas.050004797
M3 - Article
C2 - 10694577
AN - SCOPUS:4243215848
SN - 0027-8424
VL - 97
SP - 2892
EP - 2897
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 6
ER -