Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 77, Issue 1, Pages 149-163Publisher
IOS PRESS
DOI: 10.3233/JAD-200286
Keywords
Alzheimer's disease; mitochondria; mitochondrial DNA; oligomers; tau
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Funding
- University of Kansas Alzheimer's Disease Center [P30AG035982]
- Mabel A. Woodyard Foundation
- [P30 GM103326]
- [P30 CA168524]
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Background: Mitochondrial dysfunction and tau aggregation occur in Alzheimer's disease (AD), and exposing cells or rodents to mitochondrial toxins alters their tau. Objective: To further explore how mitochondria influence tau, we measured tau oligomer levels in human neuronal SH-SY5Y cells with different mitochondrial DNA (mtDNA) manipulations. Methods: Specifically, we analyzed cells undergoing ethidium bromide-induced acute mtDNA depletion, rho 0 cells with chronic mtDNA depletion, and cytoplasmic hybrid (cybrid) cell lines containing mtDNA from AD subjects. Results: We found cytochrome oxidase activity was particularly sensitive to acute mtDNA depletion, evidence of metabolic reprogramming in the rho 0 cells, anda relatively reduced mtDNA content in cybrids generated through AD subject mitochondrial transfer. In each case tau oligomer levels increased, and acutely depleted and AD cybrid cells also showed a monomer to oligomer shift. Conclusion: We conclude a cell's mtDNA affects tau oligomerization. Overlapping tau changes across three mtDNAmanipulated models establishes the reproducibility of the phenomenon, and its presence in AD cybrids supports its ADrelevance.
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