In Vitro Studies of Flemish, Dutch, and Wild-Type β-Amyloid Provide Evidence for Two-Staged Neurotoxicity

Mutations in the β-amyloid (Aβ) sequence of the amyloid precursor protein gene (APP) present with variable disease phenotypes. While patients with the Dutch APP mutation (E693Q) have predominantly hemorrhagic strokes, Flemish APP (A692G) patients develop both strokes and Alzheimer's disease (AD). To determine whether these diverse clinical and pathological presentations are due to mutant Aβ or APP, we studied the effect of Flemish, Dutch, and wild-type Aβ/APP on phosphorylation of specific tau epitopes observed in AD. No effect was observed in differentiated SH-SY5Y cells either stably express... Mehr ...