{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:18:48Z","timestamp":1790799528551,"version":"4.1.0"},"reference-count":67,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["5R01AG067617-05"],"award-info":[{"award-number":["5R01AG067617-05"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is an age-related dementia and presents a growing medical and economic burden. AD is classically diagnosed via the accumulation and aggregation of amyloid-\u03b2 and tau. Potential and FDA-approved therapies designed to clear these aggregates at best delay rather than prevent disease, indicating that the root cause of AD lay upstream of aggregate formation. Tau protein's phosphorylation is critical for AD progression, and phosphorylation at Threonine 231 is thought to be an early disease-associated, \u201cgatekeeper\u201d event.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Previously, we showed that genomic, single-copy insertion of phosphomimetic human tau (T231E) into\n                      <jats:italic toggle=\"yes\">C. elegans<\/jats:italic>\n                      mechanosensory neurons induced age-dependent deficits in light-touch sensation. Herein, we aimed to determine whether T231E tau could preferentially impact unique neuronal subclasses and whether observed deficits could be reversed via tau clearance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We generated novel\n                      <jats:italic toggle=\"yes\">C. elegans<\/jats:italic>\n                      models which express pan-neuronal human tau tagged with an auxin inducible degron and utilized an assortment of behavioral assays to assess whether specific neuronal behaviors might be impacted preferentially and whether any observed deficits could be reversed with age.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Despite our hypothesis that prolonged stress in older animals would induce irreversible metabolic rewiring or maladaptation, tau depletion rescued deficits in the behavioral response to light touch at all ages tested, including in old worms which displayed the most overt phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our data suggests that\n                      <jats:italic toggle=\"yes\">C. elegans<\/jats:italic>\n                      mechanosensory neurons are preferentially impacted by T231E, and that neuronal dysfunction induced by phosphorylated tau is reversible. This provides reassurance that current therapeutic efforts aimed at reducing soluble tau levels may prove effective.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251392935","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T18:04:11Z","timestamp":1764007451000},"page":"189-202","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Tau clearance reverses touch neuron dysfunction in both young and aged\n                    <i>C. elegans<\/i>"],"prefix":"10.1177","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5648-2772","authenticated-orcid":false,"given":"Trae A","family":"Carroll","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3464-0404","authenticated-orcid":false,"given":"Gail VW","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Nehrke","sequence":"additional","affiliation":[{"name":"Department of Medicine, Nephrology Division, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"e_1_3_3_2_2","article-title":"2025 Alzheimer's disease facts and figures","volume":"21","author":"Alzheimer's Association","year":"2025","unstructured":"Alzheimer's Association. 2025 Alzheimer's disease facts and figures. 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