Additionally, hypercholesterolemia at middle age and a high fat intake have been associated with an increased risk of AD, and use of statins, cholesterol synthesis lowering agents, have been associated with a reduced risk ( Haag et al., 2008 Wolozin, 2004) Although, the latter remains controversial and it is unlikely that statins exert their effects via an inhibition of the cholesterol synthesis rate within the brain. Apolipoprotein E (apoE) is best known for its role in cholesterol trafficking in the periphery and it is thought to exert a similar function within the central nervous system ( Pitas et al., 1987). APOE4, one of the three common isoforms of APOE, is the strongest known genetic risk factor for AD ( Corder et al., 1993). A number of the known risk factors for AD are related to cholesterol metabolism. Recent findings strengthen the link between brain cholesterol metabolism and factors involved in synaptic plasticity, a process essential for learning and memory functions. AD is a slowly progressing neurodegenerative disease that is neuropathologically characterized by senile plaques, with amyloid-β as a key protein, neurofibrillary tangles, loss of synapses, and often by vascular dysfunction and inflammatory processes. Key words: Alzheimer’s Disease / cholesterol / liver x receptors / plant sterols / memoryĪberrations in cerebral cholesterol homeostasis can lead to severe neurological diseases and have recently been linked to Alzheimer’s Disease (AD) ( Maxfield and Tabas, 2005 Tint et al., 1995 Marx, 2001 Puglielli et al., 2004). 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. Evidence is provided suggesting that brassicasterol may be a novel additional biomarker in cerebrospinal fluid of AD patients. Plant sterols may be natural activators of LXRs. Moreover, it was found that in contrast with cholesterol, the structurally very similar dietary derived plant sterols can enter the brain. 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. In contrast with what was initially assumed brain cholesterol homeostasis can be modulated by extra-cerebral factors. 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. 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). * in cerebral cholesterol homeostasis can lead to severe neurological diseases. 25, D-53127 Bonn, Germanyĭepartment of Neuroscience, Maastricht University, UniversiteitssinER, Maastrichtĭepartment of Internal Medicine, Division of Cardiovascular Diseases, Erasmus MC, ‘s-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. Tim Vanmierlo 1 ,2, Dieter Lütjohann 1 and Monique Mulder 3 *
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |