Mitochondrial function and Aβ in Alzheimer's disease postmortem brain

• Published in: Neurobiology of disease Vol. 171; p. 105781
• Main Authors: Troutwine, Benjamin R., Strope, Taylor A., Franczak, Edziu, Lysaker, Colton R., Hamid, Laylan, Mansel, Clayton, Stopperan, Julia A., Gouvion, Cynthia M., Haeri, Mohammad, Swerdlow, Russell H., Wilkins, Heather M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2022; Elsevier
• Subjects: Alzheimer's disease; Brain; Cytochrome oxidase; Mitochondria; Cytochrome oxidase; Aβ; Brain; Mitochondria; Alzheimer's disease
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2022.105781

Mitochondrial dysfunction is observed in Alzheimer's disease (AD). However, the relationship between functional mitochondrial deficits and AD pathologies is not well established in human subjects. Post-mortem human brain tissue from 11 non-demented (ND) and 12 AD subjects was used to examine mitochondrial electron transport chain (ETC) function. Data were analyzed by neuropathology diagnosis and Apolipoprotein E (APOE) genotype. Relationships between AD pathology and mitochondrial function were determined. AD subjects had reductions in brain cytochrome oxidase (COX) function and complex II Vmax. APOE ε4 carriers had COX, complex II and III deficits. AD subjects had reduced expression of Complex I-III ETC proteins, no changes were observed in APOE ε4 carriers. No correlation between p-Tau Thr 181 and mitochondrial outcomes was observed, although brains from non-demented subjects demonstrated positive correlations between Aβ concentration and COX Vmax. These data support a dysregulated relationship between brain mitochondrial function and Aβ pathology in AD. •Complex IV deficits are observed in postmortem brain samples from both Alzheimer's Disease and APOE ε4 carriers.•Complex IV function correlates with amyloid beta pathology and levels in postmortem brain.•Further analysis of mitochondrial function reveals complex II deficits in Alzheimer's Disease and APOE ε4 carriers.