title: Enhanced accumulation of tau in doubly transgenic mice expressing mutant betaAPP and presenilin-1.
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.
authors.affiliation: Department of Neurology, Division of Neuroscience, Biophysical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Samura
authors.forename: Mikio
authors.initials: M
authors.lastname: Shoji
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawarabayashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sasaki
authors.forename: Etsuro
authors.initials: E
authors.lastname: Matsubara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Murakami
authors.forename: Xu
authors.initials: X
authors.lastname: Wuhua
authors.forename: Shuta
authors.initials: S
authors.lastname: Tamura
authors.forename: Masaki
authors.initials: M
authors.lastname: Ikeda
authors.forename: Koich
authors.initials: K
authors.lastname: Ishiguro
authors.forename: Takaomi C
authors.initials: TC
authors.lastname: Saido
authors.forename: David
authors.initials: D
authors.lastname: Westaway
authors.forename: Peter
authors.initials: P
authors.lastname: St George Hyslop
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Harigaya
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008870:Microtubules / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics*; D016501:Neurites / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1; D015854:Up-Regulation / Q000235:genetics; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D053764:Presenilin-1; D016875:tau Proteins