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Role of water‐soluble amyloid‐β in the pathogenesis of Alzheimer's disease
Author(s) -
Tabaton Massimo,
Piccini Alessandra
Publication year - 2005
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.0959-9673.2005.00428.x
Subject(s) - pathogenesis , amyloid (mycology) , proteases , pathological , genetically modified mouse , disease , mutant , apolipoprotein b , alzheimer's disease , pathology , apolipoprotein e , chemistry , transgene , medicine , biochemistry , gene , enzyme , cholesterol
Summary Water‐soluble amyloid‐β (wsAβ) 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‐β (Aβ) species: 1–42, py3–42 and py11–42. The three wsAβ 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, wsAβ appears long time before amyloid deposition, indicating that it represent the first form of Aβ aggregation and accumulation. In normal brain, wsAβ is bound to apolipoprotein E that favours its degradation by proteases. The composition of wsAβ, 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 Aβ is the native counterpart of the Aβ small aggregates (soluble oligomers) that show in vitro an early and high neuronal toxicity.