title: Pathological significance of ganglioside clusters in Alzheimer's disease.
abstract: One of the key questions regarding the pathogenesis of Alzheimer's disease (AD) is how amyloid β-protein (Aβ), a proteinaceous component of senile plaques, starts to assemble into amyloid fibrils in the brain. A body of evidence is growing to suggest that Aβ binds to ganglioside on neuronal membranes, and then, is converted to an endogenous seed with an altered conformation (ganglioside-bound Aβ, GAβ) for amyloid fibril formation in the brain. Notably, the risk factors for the development of AD, including aging and apolipoprotein E4, likely facilitate the formation of ganglioside clusters in lipid raft-like membrane microdomains at pre-synaptic terminals, which provide a favorable milieu for the GAβ generation. Furthermore, it has also been suggested that endocytic pathway abnormality of neurons is involved in the formation of the ganglioside clusters. In this review, the nature of the ganglioside clusters and how gangliosides behave in the clusters leading to the GAβ generation are discussed.
authors.affiliation: Vice-Director's Research Unit, Research Institute of National Center for Geriatrics and Gerontology, Obu, Aichi, Japan. katuhiko@ncgg.go.jp
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yanagisawa
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D005732:Gangliosides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D018625:Microscopy, Atomic Force / Q000379:methods; D011485:Protein Binding / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D005732:Gangliosides