Impaired platelet mitochondrial activity in Alzheimer’s disease and mild cognitive impairment

Abstract

Mitochondrial abnormalities are found in Alzheimer's disease (AD), but previous reports haven't examined at-risk groups. In subjects with AD, mild cognitive impairment (MCI), and nondemented aged controls, platelet and lymphocyte mitochondria were isolated and analyzed for Complexes I, III, and IV of the electron transport chain. Western blots were used to control for differential enrichment of samples. Results demonstrated significant declines in Complexes III and IV in AD, and a significant decline in Complex IV in MCI. This report confirms mitochondrial deficiencies in AD, extends them to MCI, and suggests they are present at the earliest symptomatic stages of disease.

Animal model of posterior cingulate cortex hypometabolism implicated in amnestic MCI and AD

“…activity caused increased lipid peroxidation, in agreement with increasing evidence implicating C.O. inhibition and oxidative damage as neurodegenerative mechanisms in MCI and AD Benzi and Moretti, 1995;Blass et al, 2002;Mielke and Lyketsos, 2006;Reddy and Beal, 2005;Valla et al, 2001;Valla et al, 2006). The PCC may be a metabolically vulnerable brain region.…”

Mitochondria and Cell Bioenergetics: Increasingly Recognized Components and a Possible Etiologic Cause of Alzheimer's Disease

“…The AD COX defect in this study was identified through studies of platelet mitochondria. A similar finding was subsequently demonstrated in independent studies of brain, platelet, and fibroblast mitochondria (24, 31, 40, 62,144,165,176,189,204,205,240,280,281,284,292). Some researchers attributed the COX activity reduction to declining COX protein or COX subunit mRNA levels (42,43,111,145).…”

Mitochondrial DNA Oxidative Damage and Repair in Aging and Alzheimer's Disease

“…This notion is supported by an extensive literature which reports that AD is characterized by reduced cerebral energy metabolism (8), impaired activities of the tricarboxylic acid cycle enzymes (25,121,162), and defects in the mitochondrial ETC (21,32,45,146,96,193). The most consistent defect at ETC level is the decline in cytochrome c oxidase (COX) activity, an effect that is positively correlated with Ab concentration, as determined by in vitro studies (30).…”