It is well established that mitochondria play multiple critical roles including providing cellular energy, regulating apoptosis, and maintaining oxidative balance. Mitochondrial dysfunction is a hallmark of aging, chronic disease, and neurodegeneration. The purpose of this newly funded research program (NIH-R01AG027060) is to develop a comprehensive Alzheimer’s Disease and Alzheimer’s Disease Related Dementias (AD/ADRD) brain atlas of acquired mitochondrial DNA (mtDNA) mutations (heteroplasmy) across multiple brain regions and in blood from autopsy samples collected from the 50+ year Kuakini Honolulu Heart Program/Kuakini Honolulu-Asia Aging Study cohort of American men of Japanese ancestry. Identifying brain and blood heteroplasmy in a longitudinal cohort will advance the discovery of disease mechanisms related to early AD/ADRD diagnosis, neuropathology, and cognitive decline.