Benjamin R Troutwine1, Taylor A Strope2, Edziu Franczak3, Colton R Lysaker2, Laylan Hamid4, Clayton Mansel4, Julia A Stopperan4, Cynthia M Gouvion5, Mohammad Haeri5, Russell H Swerdlow6, Heather M Wilkins7. 1. University of Kansas Alzheimer's Disease Center, Kansas City, KS, USA; Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA. 2. University of Kansas Alzheimer's Disease Center, Kansas City, KS, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA. 3. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA. 4. University of Kansas Alzheimer's Disease Center, Kansas City, KS, USA. 5. University of Kansas Alzheimer's Disease Center, Kansas City, KS, USA; Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA. 6. University of Kansas Alzheimer's Disease Center, Kansas City, KS, USA; Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA. 7. University of Kansas Alzheimer's Disease Center, Kansas City, KS, USA; Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA. Electronic address: hwilkins@kumc.edu.
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.
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.
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