Enhanced accumulation of tau in doubly transgenic mice expressing mutant betaAPP and presenilin-1.
Brain Res
; 1094(1): 192-9, 2006 Jun 13.
Article
em En
| MEDLINE
| ID: mdl-16713590
ABSTRACT
Abeta amyloidosis and tauopathy are characteristic changes in the brain of Alzheimer's disease. Although much evidence suggests that Abeta deposit is a critical initiation factor, the pathological pathway between Abeta amyloidosis and tau accumulation remains unclear. Tau accumulation was examined in the doubly transgenic mouse (APP-PS) expressing betaAPP(KM670/671NL) (Tg2576) and presenilin-1 L286V (PS-1 L286Vtg). Accelerated and enhanced Abeta amyloid deposits were detected from 8 weeks. Tau accumulation appeared at 4.5 months and markedly increased in dystrophic neurites around Abeta amyloid. Accumulated tau was phosphorylated, conformationally altered, and argyrophilic. Expression of tau and accumulation of sarkosyl-insoluble phosphorylated tau were increased in APP-PS brains compared with those of Tg2576 mice. Straight or twisted tubules mimicking paired helical filament were revealed at electron microscopic level in 16-month-old APP-PS. These findings suggest that mutant presenilin-1 accelerated Abeta-induced tauopathy and further promoted fibril formation of tau.
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Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Precursor de Proteína beta-Amiloide
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Proteínas tau
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Doença de Alzheimer
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Proteínas de Membrana
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Mutação
Limite:
Animals
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article