Mitochondria alterations in fibroblasts from sporadic Alzheimer’s disease (AD) patients correlate with AD-related clinical hallmarks

Abstract

INTRODUCTIONMitochondria dysfunctions are key features in Alzheimer’s disease (AD). The occurrence of these disturbances in AD patient’s peripheral cells and their potential correlation with disease progression are under investigated.METHODSWe studied mitochondrial structure, function and mitophagy in fibroblasts including healthy volunteers and AD patients at the prodromal (AD-MCI) or demented (AD-D) stages. We carried out correlation studies with clinical cognitive scores, Aβ plaques burden and the accumulation of peripheral amyloid precursor protein C-terminal fragments (APP-CTFs).RESULTSWe unveiled progressive alteration of mitochondria structure as well as specific mitochondrial dysfunctions signatures in AD-MCI and AD-D fibroblasts and show defective mitophagy and autophagy linked to impaired lysosomal activity in AD-D fibroblasts. We reported on significant correlations of a subset of these dysfunctions with cognitive decline, AD-related clinical hallmarks and peripheral APP-CTFs accumulation.DISCUSSIONThis study emphasizes the potential use of peripheral cells for investigating AD pathophysiology and likely diagnosis.