title: Role of cholesterol in APP metabolism and its significance in Alzheimer's disease pathogenesis.
abstract: Alzheimer's disease (AD) is a complex multifactorial neurodegenerative disorder believed to be initiated by accumulation of amyloid β (Aβ)-related peptides derived from proteolytic processing of amyloid precursor protein (APP). Research over the past two decades provided a mechanistic link between cholesterol and AD pathogenesis. Genetic polymorphisms in genes regulating the pivotal points in cholesterol metabolism have been suggested to enhance the risk of developing AD. Altered neuronal membrane cholesterol level and/or subcellular distribution have been implicated in aberrant formation, aggregation, toxicity, and degradation of Aβ-related peptides. However, the results are somewhat contradictory and we still do not have a complete understanding on how cholesterol can influence AD pathogenesis. In this review, we summarize our current understanding on the role of cholesterol in regulating the production/function of Aβ-related peptides and also examine the therapeutic potential of regulating cholesterol homeostasis in the treatment of AD pathology.
authors.affiliation: Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada, T6G 2M8.
authors.forename: M
authors.initials: M
authors.lastname: Maulik
authors.forename: D
authors.initials: D
authors.lastname: Westaway
authors.forename: J H
authors.initials: JH
authors.lastname: Jhamandas
authors.forename: S
authors.initials: S
authors.lastname: Kar
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008969:Molecular Sequence Data
chemical_list: D016564:Amyloid beta-Protein Precursor; D002784:Cholesterol