How would preclinical Alzheimer's disease (AD pathology) occur? An insight from a genomic instability mouse model

摘要

More than 95%of Alzheimer’s disease(AD)is late-onset,in which patients show clinical cognition/behavior symptoms after age 65.Unlike early-onset AD that comes with mutations in genes directly involved in amyloid metabolism(APP,PSEN),genetic predispositions associated with late-onset AD are harder to pinpoint,and their mechanistic links to AD development need further investigation.Although the development mechanism of late-onset AD remains controversial,amyloid-beta accumulation,initiated in middle age,is widely accepted as the triggering event for early AD pathology(Du Bois et al.,2010;Sterling et al.,2011).