title: Cholesterol-dependent aggregation of amyloid beta-protein.
abstract: One of the fundamental pathological processes of Alzheimer's disease (AD) is the aggregation of the amyloid beta-protein (Abeta). In the case of familial AD, the expression of genes responsible for this disease is likely to enhance aggregation of Abeta through its enhanced generation. However, there is no evidence to indicate thus far that in the case of sporadic AD, a major form of the disease, the generation of Abeta is altered. Thus, one could assume that the aggregation of Abeta in AD is induced by unknown posttranslational modification or by an altered clearance mechanism, or both. We previously identified a novel Abeta species in the human brain that exhibited early pathological changes of AD. This Aalpha is characterized by its tight binding to GM1 ganglioside (GM1). Based on its unique molecular characteristics, including its extremely high aggregation potential and altered immunoreactivity, we hypothesized that Abeta undergoes conformational alteration and acts as a seed for Abeta fibrillogenesis. In regard to the molecular mechanism underlying the formation of GM1-Abeta, we recently found that binding of Abeta to GM1 was facilitated in cholesterol-rich environments and, furthermore, it was dependent on the cholesterol-induced clustering of GM1 in the host membranes. Recently, increasing evidence indicates that cholesterol is a risk factor for AD development. The results of our current studies may provide a new insight into the molecular mechanism underlying the cholesterol-dependent development of AD.
authors.affiliation: Department of Dementia Research, National Institute for Longevity Sciences, 36-3 Gengo, Morioka, Obu 474-8522, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yanagisawa
authors.forename: Katsumi
authors.initials: K
authors.lastname: Matsuzaki
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans
chemical_list: D016229:Amyloid beta-Peptides; D002784:Cholesterol