TY - JOUR
T1 - Enhanced accumulation of tau in doubly transgenic mice expressing mutant βAPP and presenilin-1
AU - Samura, Eriko
AU - Shoji, Mikio
AU - Kawarabayashi, Takeshi
AU - Sasaki, Atsushi
AU - Matsubara, Etsuro
AU - Murakami, Tetsuro
AU - Wuhua, Xu
AU - Tamura, Shuta
AU - Ikeda, Masaki
AU - Ishiguro, Koich
AU - Saido, Takaomi C.
AU - Westaway, David
AU - St. George Hyslop, Peter
AU - Harigaya, Yasuo
AU - Abe, Koji
N1 - Funding Information:
This work was supported by Grants-in Aid for Primary Amyloidosis Research Committee (S. Ikeda and T. Ishihara); surveys and research on special disease from the Ministry of Health, Labor and Welfare of Japan and by Grants-in Aid for Scientific Research (B) (16390251, 15390273), Scientific Research (C) (16590829, 15590879 and 16500213), and Scientific Research on Priority Areas (C) – Advanced Brain Science Project – from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
PY - 2006/6/13
Y1 - 2006/6/13
N2 - Aβ amyloidosis and tauopathy are characteristic changes in the brain of Alzheimer's disease. Although much evidence suggests that Aβ deposit is a critical initiation factor, the pathological pathway between Aβ amyloidosis and tau accumulation remains unclear. Tau accumulation was examined in the doubly transgenic mouse (APP-PS) expressing βAPPKM670/671NL (Tg2576) and presenilin-1 L286V (PS-1 L286Vtg). Accelerated and enhanced Aβ amyloid deposits were detected from 8 weeks. Tau accumulation appeared at 4.5 months and markedly increased in dystrophic neurites around Aβ 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 Aβ-induced tauopathy and further promoted fibril formation of tau.
AB - Aβ amyloidosis and tauopathy are characteristic changes in the brain of Alzheimer's disease. Although much evidence suggests that Aβ deposit is a critical initiation factor, the pathological pathway between Aβ amyloidosis and tau accumulation remains unclear. Tau accumulation was examined in the doubly transgenic mouse (APP-PS) expressing βAPPKM670/671NL (Tg2576) and presenilin-1 L286V (PS-1 L286Vtg). Accelerated and enhanced Aβ amyloid deposits were detected from 8 weeks. Tau accumulation appeared at 4.5 months and markedly increased in dystrophic neurites around Aβ 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 Aβ-induced tauopathy and further promoted fibril formation of tau.
KW - Alzheimer's disease
KW - Aβ
KW - Doubly transgenic mouse
KW - Presenilin-1
KW - Tau
KW - Tg2576
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U2 - 10.1016/j.brainres.2005.12.134
DO - 10.1016/j.brainres.2005.12.134
M3 - Article
C2 - 16713590
AN - SCOPUS:33745258680
SN - 0006-8993
VL - 1094
SP - 192
EP - 199
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 1
ER -