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Myelinating oligodendrocytes may represent a metabolically vulnerable hub linking these processes to circuit dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We assessed human hippocampal tissue by immunofluorescence and profiled THY\u2010Tau22 mice using diffusion tensor imaging, metabolomics, lipidomics, and single\u2010nucleus RNA sequencing. Symptomatic mice were treated with the equilibrative nucleoside transporter 1 (ENT1) inhibitor J4 to evaluate therapeutic modulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Hippocampal tissue from patients with tauopathy showed reduced oligodendrocyte\u2010 and myelin\u2010associated CNPase signal. THY\u2010Tau22 mice exhibited progressive reductions in hippocampal\u2013prefrontal fractional anisotropy, myelin\u2010associated alterations, purine and lipid metabolic remodeling, and oligodendrocyte\u2010enriched lipid\u2010associated transcriptional changes. J4 treatment selectively modulated purine and lipid metabolic pathways and improved myelin\u2010associated markers and structural connectivity measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>ENT1 inhibition links adenosine homeostasis to oligodendrocyte\u2010associated metabolic pathways and supports further investigation as a potential therapeutic approach for tauopathy\u2010associated network dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71789","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:00:11Z","timestamp":1789124411000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ENT1 inhibition links oligodendrocyte lipid metabolism to connectivity in tauopathy"],"prefix":"10.1002","volume":"22","author":[{"given":"Ching\u2010Pang","family":"Chang","sequence":"first","affiliation":[{"name":"Institute of Biomedical Sciences Academia Sinica  Taipei Taiwan"},{"name":"Biomedical Translation Research Center Academia Sinica  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Wen","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Wen","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences Academia Sinica  Taipei Taiwan"},{"name":"Biomedical Translation Research Center Academia Sinica  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian Jing","family":"Siew","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences Academia Sinica  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Blum","sequence":"additional","affiliation":[{"name":"UMR\u2010S1172 \u2010 LilNCog \u2010 Lille Neuroscience &amp; Cognition Univ. Lille, Inserm, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee\u2010Way","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of California Davis  Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You\u2010Yin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"International Ph.D. Program in Medicine, College of Medicine Taipei Medical University  New Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijuang","family":"Chern","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences Academia Sinica  Taipei Taiwan"},{"name":"Biomedical Translation Research Center Academia Sinica  Taipei 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