In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 6 ( 2000-03-14), p. 2892-2897
Abstract:
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 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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.050004797
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2000
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12