Chapter 7: Folding and Misfolding of Amyloid-β40 and 42 in Alzheimer’s Disease

The major component of senile plaques, the hallmark in the brain of patients with Alzheimer’s disease (AD), is fibrillar amyloid-β(Aβ). Aβ is an intrinsically disordered peptide proteolyzed from amyloid precursor protein (APP). Several familial mutations that may cause the early onset of AD are within and around Aβ sequence. It demonstrates the importance of understanding folding and misfolding mechanisms of Aβ. Here, we summarize our previous works starting from examining folding stability of the initial state of Aβ42 and Aβ40, and comparing the relationship of folding stability among wild-type Aβ and familial AD (FAD) mutants to their misfolding properties. We also showed that zinc and aluminumions destabilize Aβ and result in oligomer formation. Finally, we systematically examine the fibrillization kinetics and induced cytotoxicity among various mixtures of Aβ42/Aβ40.