In vitro studies of amyloid β-protein fibril assembly and toxicity provide clues to the aetiology of Flemish variant (Ala692 → Gly) Alzheimer's disease

In a Flemish kindred, an Ala692 → Gly amino acid substitution in the amyloid β-protein precursor (AβPP) causes a form of early-onset Alzheimer's disease (AD)which displays prominent amyloid angiopathy and unusually large senile plaque cores. The mechanistic basis of this Flemish form of AD is unknown. Previous in vitro studies of amyloid β-protein (Aβ) production in HEK-293 cells transfected with cDNA encoding Flemish AβPP have shown that full-length [Aβ(1-40)]and truncated [Aβ(5-40) and Aβ(11-40)] forms of Aβ are produced. In an effort to determine how these peptides might contribute to the p... Mehr ...