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

Eriko Samura, Mikio Shoji, Takeshi Kawarabayashi, Atsushi Sasaki, Etsuro Matsubara, Tetsuro Murakami, Xu Wuhua, Shuta Tamura, Masaki Ikeda, Koich Ishiguro, Takaomi C. Saido, David Westaway, Peter St. George Hyslop, Yasuo Harigaya, Koji Abe

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)192-199
Number of pages8
JournalBrain Research
Volume1094
Issue number1
DOIs
Publication statusPublished - Jun 13 2006

Keywords

  • Alzheimer's disease
  • Doubly transgenic mouse
  • Presenilin-1
  • Tau
  • Tg2576

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Enhanced accumulation of tau in doubly transgenic mice expressing mutant βAPP and presenilin-1'. Together they form a unique fingerprint.

  • Cite this

    Samura, E., Shoji, M., Kawarabayashi, T., Sasaki, A., Matsubara, E., Murakami, T., Wuhua, X., Tamura, S., Ikeda, M., Ishiguro, K., Saido, T. C., Westaway, D., St. George Hyslop, P., Harigaya, Y., & Abe, K. (2006). Enhanced accumulation of tau in doubly transgenic mice expressing mutant βAPP and presenilin-1. Brain Research, 1094(1), 192-199. https://doi.org/10.1016/j.brainres.2005.12.134