Enhanced accumulation of tau in doubly transgenic mice expressing mutant betaAPP and presenilin-1

• Published in: Brain research 2006-06, Vol.1094 (1), p.192-199
• Main Authors: Samura, Eriko, Shoji, Mikio, Kawarabayashi, Takeshi, Sasaki, Atsushi, Matsubara, Etsuro, Murakami, Tetsuro, Wuhua, Xu, Tamura, Shuta, Ikeda, Masaki, Ishiguro, Koich, Saido, Takaomi C, Westaway, David, St George Hyslop, Peter, Harigaya, Yasuo, Abe, Koji
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Animals; Brain - metabolism; Brain - pathology; Brain - physiopathology; Disease Models, Animal; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Transgenic; Microscopy, Electron, Transmission; Microtubules - metabolism; Microtubules - pathology; Microtubules - ultrastructure; Mutation - genetics; Neurites - metabolism; Neurites - pathology; Neurites - ultrastructure; Neurofibrillary Tangles - genetics; Neurofibrillary Tangles - metabolism; Neurofibrillary Tangles - pathology; Phosphorylation; Plaque, Amyloid - genetics; Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; Presenilin-1; tau Proteins - metabolism; Up-Regulation - genetics
• ISSN: 0006-8993

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.