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dc.contributor.authorWeidling, Ian W.
dc.contributor.authorWilkins, Heather M.
dc.contributor.authorKoppel, Scott J.
dc.contributor.authorHutfles, Lewis
dc.contributor.authorWang, Xiaowan
dc.contributor.authorKalani, Anuradha
dc.contributor.authorMenta, Blaise W.
dc.contributor.authorRyan, Benjamin
dc.contributor.authorPerez-Ortiz, Judit
dc.contributor.authorGamblin, Chris
dc.contributor.authorSwerdlow, Russell H.
dc.date.accessioned2022-01-20T16:24:49Z
dc.date.available2022-01-20T16:24:49Z
dc.date.issued2020-06-02
dc.identifier.citationWeidling, I. W., Wilkins, H. M., Koppel, S. J., Hutfles, L., Wang, X., Kalani, A., Menta, B. W., Ryan, B., Perez-Ortiz, J., Gamblin, T. C., & Swerdlow, R. H. (2020). Mitochondrial DNA Manipulations Affect Tau Oligomerization. Journal of Alzheimer's disease : JAD, 77(1), 149–163. https://doi.org/10.3233/JAD-200286en_US
dc.identifier.urihttp://hdl.handle.net/1808/32459
dc.description.abstractBackground: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, ρ0 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 re-programming in the ρ0 cells, and a 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 mtDNA-manipulated models establishes the reproducibility of the phenomenon, and its presence in AD cybrids supports its AD-relevance.en_US
dc.publisherIOS Pressen_US
dc.rightsCopyright 2020 The Author(s).en_US
dc.subjectAlzheimer’s diseaseen_US
dc.subjectMitochondriaen_US
dc.subjectMitochondrial DNAen_US
dc.subjectOligomersen_US
dc.subjectTauen_US
dc.titleMitochondrial DNA Manipulations Affect Tau Oligomerizationen_US
dc.typeArticleen_US
kusw.kuauthorGamblin, T. Chris
kusw.kudepartmentMolecular Biosciencesen_US
dc.identifier.doi10.3233/JAD-200286en_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC7962146en_US
dc.rights.accessrightsopenAccessen_US


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