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 βAPP KM670/671NL (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.
