Volume 18, Number 4, Juillet-Août 2011Lipids and Brain II. Actes des Journées Chevreul 2011 (Première partie)
|Page(s)||214 - 217|
|Section||PUFA, Cholesterol and Alzheimer Diseases|
|Published online||15 July 2011|
Brain cholesterol in normal and pathological aging
Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany
2 Department of Neuroscience, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht
3 Department of Internal Medicine, Division of Cardiovascular Diseases, Erasmus MC, ‘s-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
Aberrations in cerebral cholesterol homeostasis can lead to severe neurological diseases. Recent findings strengthen the link between brain cholesterol metabolism and factors involved in synaptic plasticity, a process essential for learning and memory functions, as well as regeneration, which are affected in Alzheimer’s Disease (AD). Cholesterol homeostasis within the brain is independent of that in the rest of the body and needs to be strictly regulated for optimal brain functioning. In contrast with what was initially assumed brain cholesterol homeostasis can be modulated by extra-cerebral factors. We have found that enhancement of the cholesterol-turnover in the brain by administration of the synthetic activator of liver x receptos (LXRs), T0901317, leads to restoration of memory functions in an AD mouse-model.Memory in C57Bl6NCrl mice was not further improved by the same treatment. Moreover, it was found that in contrast with cholesterol, the structurally very similar dietary derived plant sterols can enter the brain. Plant sterols may be natural activators of LXRs. Evidence is provided suggesting that brassicasterol may be a novel additional biomarker in cerebrospinal fluid of AD patients. Insight into the regulation of cerebral cholesterol homeostasis will provide possibilities to modulate the key steps involved and may lead to the development of therapies for the prevention as well as treatment of neurodegenerative diseases such as AD.
Key words: Alzheimer’s Disease / cholesterol / liver x receptors / plant sterols / memory
© John Libbey Eurotext 2011
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