Alzheimer's protection effect of A673T mutation may be driven by lower Aβ oligomer binding affinity.

ABSTRACT: Several mutations conferring protection against Alzheimer's disease (AD) have been described, none as profound as the A673T mutation, where carriers are four times less likely to get AD compared to noncarriers. This mutation results in reduced amyloid beta (Aβ) protein production in vitro and lower lifetime Aβ concentration in carriers. Better understanding of the protective mechanisms of the mutation may provide important insights into AD pathophysiology and identify productive therapeutic intervention strategies for disease modification. Aβ(1-42) protein forms oligomers that bind saturably to a single receptor site on neuronal synapses, initiating the downstream toxicities observed in AD. Decreased formation, toxicity, or stability of soluble Aβ oligomers, or reduction of synaptic bindin

SUBMITTER: Limegrover CS 

PROVIDER: S-EPMC8246829 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature