Mitochondrial function and Aβ in Alzheimer's disease postmortem brain
Benjamin Troutwine, Taylor A. Strope, Edziu Franczak, Colton R Lysaker, Laylan Hamid, Clayton Mansel, Julia A. Stopperan, Cynthia M. Gouvion, Mohammad Haeri, Russell H. Swerdlow, Heather Wilkins
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: These data support a dysregulated relationship between brain mitochondrial function and Aβ pathology in AD.