Electron transport chain defects in Alzheimer's disease brain

TLDR

Previous work suggested a deficiency in the terminal complex of the mitochondrial electron transport chain, cytochrome c oxidase (COX), in platelet mitochondria of Alzheimer’s disease patients. The study aims to determine whether Alzheimer’s disease brain mitochondria also exhibit COX deficiency by assaying electron transport chain activities. Mitochondria were isolated from autopsied brain tissue of 9 AD patients and 8 controls, and activities of all electron transport chain complexes were measured. All complexes were depressed in AD brain, with the greatest reduction in COX activity, while cytochrome concentrations remained unchanged, indicating a COX‑centered defect.

Abstract

Previous work suggested a deficiency in the terminal complex of the mitochondrial electron transport chain, cytochrome <i>c</i> oxidase (COX), in platelet mitochondria of Alzheimer9s disease (AD) patients. The present study extends this observation to AD brain mitochondria through assay of electron transport chain activities in mitochondria isolated from autopsied brain samples from AD patients (n = 9) and from controls with and without known neurologic disease (n = 8). AD brain mitochondria demonstrated a generalized depression of activity of all electron transport chain complexes. This depression was most marked in COX activity (<i>p</i> &lt; 0.001). Concentrations of cytochromes <i>b, c₁</i> and <i>aa₃</i> were similar in AD and controls. The electron transport chain is defective in AD brain, and the defect centers about COX.