Format

Send to

Choose Destination
See comment in PubMed Commons below
Neurobiol Dis. 2000 Aug;7(4):321-31.

Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model.

Author information

1
Nathan S. Kline Institute for Dementia Research, Orangeburg, New York, USA. refolo@nki.rfmh.org

Erratum in

  • Neurobiol Dis 2000 Dec;7(6 Pt B):690.

Abstract

Recent data suggest that cholesterol metabolism is linked to susceptibility to Alzheimer's disease (AD). However, no direct evidence has been reported linking cholesterol metabolism and the pathogenesis of AD. To test the hypothesis that amyloid beta-peptide (Abeta) deposition can be modulated by diet-induced hypercholesterolemia, we used a transgenic-mouse model for AD amyloidosis and examined the effects of a high-fat/high-cholesterol diet on central nervous system (CNS) Abeta accumulation. Our data showed that diet-induced hypercholesterolemia resulted in significantly increased levels of formic acid-extractable Abeta peptides in the CNS. Furthermore, the levels of total Abeta were strongly correlated with the levels of both plasma and CNS total cholesterol. Biochemical analysis revealed that, compared with control, the hypercholesterolemic mice had significantly decreased levels of sAPPalpha and increased levels of C-terminal fragments (beta-CTFs), suggesting alterations in amyloid precursor protein processing in response to hypercholesterolemia. Neuropathological analysis indicated that the hypercholesterolemic diet significantly increased beta-amyloid load by increasing both deposit number and size. These data demonstrate that high dietary cholesterol increases Abeta accumulation and accelerates the AD-related pathology observed in this animal model. Thus, we propose that diet can be used to modulate the risk of developing AD.

PMID:
10964604
DOI:
10.1006/nbdi.2000.0304
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center