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Biology Articles » Neurobiology » Molecular & Cellular Neurobiology » Amyloid beta, neural lipids, cholesterol & Alzheimer's disease » Cholesterol is the possible cause of neurodegeneration in AD

Cholesterol is the possible cause of neurodegeneration in AD
- Amyloid beta, neural lipids, cholesterol & Alzheimer's disease


In a separate set of experiments by modifying rat cholesterol status with the diet containing 2 % cholesterol for several months we generated animal model, that expressed brain amyloid similar to amyloid deposition of Alzheimer's disease brain specimens [4, 6, fr3, fr4, fr5]. We then prepared slices from the hippocampus, maintained them live in vitro, and subjected to the study of cholesterol synthesis by labeling with radioactive acetate. After labeling the lipids were extracted from slices, separated by thin layer chromatography, and quantitated by radioactivity counting. This methodology allowed us to quantitate the higher rate of cholesterol and phospholipids synthesis in rats fed a cholesterol diet, and to conclude that brain cholesterol synthesis upregulation is a possible cause (but NOT a consequence) of Alzheimer's-like brain amyloid. Most important, we also performed electrophysiological analysis of slices. We found that cholesterol-fed rats lack hippocampal LTP and thus have impaired synaptic plasticity [4, 6] It is notable that impaired LTP could be reversed by the reversal of a 2% cholesterol diet to a regular diet for an extended period of time. It is in accord with the notion that the rate of cholesterol turnover in the brain is very low, and thus requires long time for a disturbance (or a correction in case of the opposite order of events) to yield appreciable change. Our functional analysis data significantly extended several earlier histochemical reports that demonstrated amyloid buildup in rabbits and in amyloid precursor protein transgenic mice fed a cholesterol diet (see Refs. 4, 5, 6 for details).

CHOLESTEROL, AMYLOID b AND ALZHEIMER’S CSF-HDL

Our other study [3] showed that Alzheimer’s patients have unique pattern of HDL distribution in the CSF, the lipoprotein fraction that is especially important in cholesterol transport in tissue environment and across the body, and that has soluble form of Ab as an apolipoprotein constituent [1]. Particularly we observed an increase in content of soluble Ab and selected apolipoproteins in the HDL subfraction called HDL1. Remembering a special role for HDL1 in reverse cholesterol transport on one hand, and the role for Ab in cholesterol esterification (that causes HDL size change and the formation of HDL1, Ref.3) we interpreted our data as an additional piece in Alzheimer’s cholesterol puzzle [3, 4].


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