Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease

DM Holtzman, KR Bales, T Tenkova… - Proceedings of the …, 2000 - National Acad Sciences
DM Holtzman, KR Bales, T Tenkova, AM Fagan, M Parsadanian, LJ Sartorius, B Mackey…
Proceedings of the National Academy of Sciences, 2000National Acad Sciences
Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (ɛ4> ɛ3) 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 APPV717F transgenic (TG) mice
expressing mouse, human, or no apoE (apoE−/−). A severe, plaque-associated neuritic
dystrophy developed in APPV717F TG mice expressing mouse or human apoE. Though …
Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (ɛ4 > ɛ3) 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 APPV717F transgenic (TG) mice expressing mouse, human, or no apoE (apoE−/−). A severe, plaque-associated neuritic dystrophy developed in APPV717F TG mice expressing mouse or human apoE. Though significant levels of Aβ deposition also occurred in APPV717F TG, apoE−/− mice, neuritic degeneration was virtually absent. Expression of apoE3 and apoE4 in APPV717F 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 APPV717F TG mice. Our data demonstrate a critical and isoform-specific role for apoE in neuritic plaque formation, a pathological hallmark of AD.
National Acad Sciences