Journal
ALZHEIMERS & DEMENTIA
Volume 19, Issue 5, Pages 2069-2083Publisher
WILEY
DOI: 10.1002/alz.12812
Keywords
Alzheimer's disease; haplogroup; mitochondrial DNA copy number; mitochondrial dysfunction; mitochondrial genome abundance; mitochondrial heteroplasmy
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Mitochondrial dysfunction is an early and prominent feature of Alzheimer's disease, which affects neuronal and glial cell function by reducing mitochondrial bioenergetics. It is still unknown whether mitochondrial dysfunction causes, mediates, or is a by-product of AD pathogenesis.
Mitochondrial dysfunction is an early and prominent feature of Alzheimer's disease (AD), with impaired energy metabolism preceding the onset of clinical symptoms. Here we propose an update to the mitochondrial dysfunction hypothesis of AD based on recent results examining the role of mitochondrial genome abundance in AD. In a large post mortem study, we show that lower brain mitochondrial genome abundance is associated with a greater odds of AD neuropathological change and worse cognitive performance. We hypothesize that lower mitochondrial genome abundance impairs mitochondrial function by reducing mitochondrial bioenergetics, thereby impacting neuronal and glial cell function. However, it remains to be determined if mitochondrial dysfunction causes, mediates, or is a by-product of AD pathogenesis. Additional support for this hypothesis will be generated by linking peripheral blood mitochondrial genome abundance to AD and establishing clinical trials of compounds that upregulate total mitochondrial genome abundance or boost mitochondrial mass.
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