Mitochondria-sequestered Aβ renders synaptic mitochondria vulnerable in the elderly with a risk of Alzheimer disease.

ABSTRACT: Mitochondria are critical for neurophysiology, and mitochondrial dysfunction constitutes a characteristic pathology in both brain aging and Alzheimer disease (AD). Whether mitochondrial deficiency in brain aging and AD is mechanistically linked, however, remains controversial. We report a correlation between intrasynaptosomal amyloid β 42 (Aβ42) and synaptic mitochondrial bioenergetics inefficiency in both aging and amnestic mild cognitive impairment, a transitional stage between normal aging and AD. Experiments using a mouse model expressing nonmutant humanized Aβ (humanized Aβ-knockin [hAβ-KI] mice) confirmed the association of increased intramitochondrial sequestration of Aβ42 with exacerbated synaptic mitochondrial dysfunction in an aging factor- and AD risk-bearing context. Also, in c

SUBMITTER: Jia K 

PROVIDER: S-EPMC10721326 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature