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Exp Neurol. 2006 Aug;200(2):460-7. Epub 2006 May 11.

High cholesterol content in neurons increases BACE, beta-amyloid, and phosphorylated tau levels in rabbit hippocampus.

Author information

1
Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, 58202, USA. oghribi@medicine.nodak.edu

Abstract

Epidemiological, cellular, and animal studies suggest that abnormalities in cholesterol metabolism may contribute to the etiology of Alzheimer's disease by increasing the generation of beta-amyloid (Abeta). However, the mechanism by which cholesterol increases Abeta levels is not fully understood. In the present study, we demonstrate that feeding rabbits with 1% cholesterol for 7 months causes an increase in cholesterol content in neurons. High cholesterol content in neurons is accompanied by an increase in the level of BACE1, the enzyme that initially cleaves beta-amyloid precursor protein to generate Abeta, causing the accumulation of Abeta1-42 peptide. These effects correlate with the phosphorylation of tau and the activation of extracellular signal-regulated protein kinase (ERK). Our data suggest that excessive cholesterol content in neurons, following long-term dietary cholesterol, may underlie the increase in BACE1 and Abeta levels. Increased Abeta levels may in turn trigger the phosphorylation of tau by activating ERK.

PMID:
16696972
DOI:
10.1016/j.expneurol.2006.03.019
[Indexed for MEDLINE]

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