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Does cholesterol act as a protector of cholinergic projections in Alzheimer's disease?

Lookup NU author(s): Dr Iwo Bohr



The relationship between Alzheimer's disease (AD) and progressive degeneration of the forebrain cholinergic system is very well established, whereas mechanisms linking this disease with cholesterol, apolipoprotein E (apoE) phenotype, and amyloid precursor protein (APP) metabolism have not been fully elucidated even though there is a plethora of publications separately on each of these issues. The intention of this hypothesis is to unify knowledge coming from all of these areas. It is based on an assumption that the process of APP hypermetabolism is a neuroprotective response for age-related cholinergic deterioration. In some individuals this initially positive process becomes highly overregulated by genetic or/and epigenetic risk factors and after many years of accumulations lead eventually to AD. I hypothesise that neuroprotective role of APP-hypermetabolism might be related to enrichment of neuronal membranes (lipid rafts in particular) in cholesterol in order to compensate for decrease in presynaptic cholinergic transmission and/or AD-related decrease in cholesterol levels. The above is consistent with findings indicating that activity of both muscarinic and nicotinic cholinergic receptors is correlated in a positive manner with cholesterol plasmalemmal content. Briefly - APP metabolism together with transport of cholesterol in apoE containing lipoproteins seem to play a key role in mobilising cholesterol into neuronal membranes. © 2005 Bohr; licensee BioMed Central Ltd.

Publication metadata

Author(s): Bohr IJ

Publication type: Article

Publication status: Published

Journal: Lipids in Health and Disease

Year: 2005

Volume: 4

Pages: 13

Date deposited: 27/05/2010

ISSN (electronic): 1476-511X

Publisher: BioMed Central Ltd.


DOI: 10.1186/1476-511X-4-13

Notes: Article no. 13


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