Role of water-soluble amyloid-beta in the pathogenesis of Alzheimer's disease.
Water-soluble amyloid-beta (wsAbeta) is present in cerebral cortex of subjects at risk of Alzheimer's disease (AD) as well as in normal elderly subjects as a mixture of three major amyloid-beta (Abeta) species: 1-42, py3-42 and py11-42. The three wsAbeta species are nondetectable in brains of young people, free of immunohistochemically detectable amyloid plaques. In the brains of Down's syndrome and APP-mutant transgenic mice, wsAbeta appears long time before amyloid deposition, indicating that it represent the first form of Abeta aggregation and accumulation. In normal brain, wsAbeta is bound to apolipoprotein E that favours its degradation by proteases. The composition of wsAbeta, in terms of the ratio between the full-length 1-42 and the py3-42 peptides, correlates with the severity of clinical and pathological phenotype in familial early onset AD. Water-soluble Abeta is the native counterpart of the Abeta small aggregates (soluble oligomers) that show in vitro an early and high neuronal toxicity.
Tabaton
Massimo
M
Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Via De Toni 5, 16132 Genoa, Italy. mtabaton@neurologia.unige.it
Piccini
Alessandra
A
D000544:Alzheimer Disease / Q000209:etiology* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008657:Metabolic Clearance Rate; D051379:Mice; D010641:Phenotype; D012995:Solubility; D014867:Water
D016229:Amyloid beta-Peptides; D014867:Water