Document Detail


Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease.
MedLine Citation:
PMID:  15716586     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Extracellular amyloid plaques, intracellular neurofibrillary tangles, and loss of basal forebrain cholinergic neurons in the brains of Alzheimer's disease (AD) patients may be the end result of abnormalities in lipid metabolism and peroxidation that may be caused, or exacerbated, by beta-amyloid peptide (Abeta). Apolipoprotein E (apoE) is a major apolipoprotein in the brain, mediating the transport and clearance of lipids and Abeta. ApoE-dependent dendritic and synaptic regeneration may be less efficient with apoE4, and this may result in, or unmask, age-related neurodegenerative changes. The increased risk of AD associated with apoE4 may be modulated by diet, vascular risk factors, and genetic polymorphisms that affect the function of other transporter proteins and enzymes involved in brain lipid homeostasis. Diet and apoE lipoproteins influence membrane lipid raft composition and the properties of enzymes, transporter proteins, and receptors mediating Abeta production and degradation, tau phosphorylation, glutamate and glucose uptake, and neuronal signal transduction. The level and isoform of apoE may influence whether Abeta is likely to be metabolized or deposited. This review examines the current evidence for diet, lipid homeostasis, and apoE in the pathogenesis of AD. Effects on the cholinergic system and response to cholinesterase inhibitors by APOE allele carrier status are discussed briefly.
Authors:
Roger M Lane; Martin R Farlow
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Publication Detail:
Type:  Journal Article; Review     Date:  2005-02-16
Journal Detail:
Title:  Journal of lipid research     Volume:  46     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-18     Completed Date:  2005-11-01     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  949-68     Citation Subset:  IM    
Affiliation:
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. roger.lane@pharma.novartis.com
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MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / metabolism*,  pathology
Apolipoproteins E / metabolism*
Diet
Homeostasis*
Humans
Lipid Metabolism*
Lipid Peroxidation
Chemical
Reg. No./Substance:
0/Apolipoproteins E

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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