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Woodyard Memorial Fellowship Fund"],"award-info":[{"award-number":["Mabel A. Woodyard Memorial Fellowship Fund"]}],"id":[{"id":"https:\/\/ror.org\/001tmjg57","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG061194"],"award-info":[{"award-number":["R01 AG061194"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Snyder Family Foundation"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In Alzheimer's disease (AD), tau protein aggregates to form neurofibrillary tangles (NFTs). The cellular changes favoring AD brain NFT formation remain incompletely understood. AD brains also display mitochondrial defects, including reduced mitochondrial DNA (mtDNA) copy number.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We considered whether mtDNA depletion alters tau homeostasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We assessed tau mRNA using short-read mRNA sequencing and PCR, and tau protein using immunochemistry, in SH-SY5Y cells with chronic mtDNA depletion (\u03c10).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      mtDNA depletion increased tau expression and resulted in alternatively spliced isoforms, elevated 4R and exon 4a-containing\n                      <jats:italic toggle=\"yes\">MAPT<\/jats:italic>\n                      transcripts, and consistently detectable big tau protein. \u03c10 cells also displayed an elevated\n                      <jats:italic toggle=\"yes\">MAPT<\/jats:italic>\n                      exon 13 3\u2019Untranslated Region (UTR): Coding DNA sequence (CDS) ratio. Phosphorylation at amino acid positions 217 and 181 decreased.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Mitochondrial dysfunction affects tau expression, splicing, and 3\u2019UTR retention while increasing tau protein levels and modifying its phosphorylation. These studies hold AD relevance as they provide evidence for a relationship between two AD-associated phenomena, defective mitochondrial function and altered\n                      <jats:italic toggle=\"yes\">MAPT<\/jats:italic>\n                      regulation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261492673","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:44:01Z","timestamp":1790682241000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic mitochondrial DNA depletion alters\n                    <i>MAPT<\/i>\n                    splicing and increases tau levels"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5277-7149","authenticated-orcid":false,"given":"Ian","family":"Weidling","sequence":"first","affiliation":[{"name":"University of Kansas Alzheimer\u2019s Disease Research 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