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However, its role in tau pathology remains unknown. Here, we demonstrate that WAVE1 activity is suppressed in P301S tau mice through elevated inhibitory phosphorylation. Strikingly, WAVE1 gene (\n                  <jats:italic>Wasf1<\/jats:italic>\n                  ) knockout in P301S tau mice significantly reduces tau hyperphosphorylation and improves cognition, suggesting a compensatory role for WAVE1 suppression in tau pathogenesis. Single-nucleus RNA sequencing reveals that\n                  <jats:italic>Wasf1<\/jats:italic>\n                  deletion in P301S tau mice reverses microglial state transitions, with minimal impact on other brain cell types.\n                  <jats:italic>Wasf1<\/jats:italic>\n                  mRNA is highly translated in microglia in non-Tg mice, while its expression is downregulated in P301S tau mice.\n                  <jats:italic>Wasf1<\/jats:italic>\n                  knockdown in BV2 microglia cells enhances the degradation of engulfed tau fibrils, indicating WAVE1 as an endogenous regulator of microglial function. Additionally, CellChat analysis indicates that\n                  <jats:italic>Wasf1<\/jats:italic>\n                  deletion alters microglial autocrine signaling and their interactions with other cell types in P301S tau mice. These findings, taken together, suggest that\n                  <jats:italic>Wasf1<\/jats:italic>\n                  deletion restores homeostatic microglial function, mitigates tau pathology, and alleviates cognitive deficits, highlighting WAVE1 as a potential therapeutic target for tauopathy-related dementias.\n                <\/jats:p>","DOI":"10.64898\/2026.01.14.699391","type":"posted-content","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:45:20Z","timestamp":1768506320000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Wasf1<\/i>\n                  deletion attenuates tau hyperphosphorylation, microglial state transition, and cognitive deficits in P301S tau mice"],"prefix":"10.64898","author":[{"given":"Clara","family":"Berdasco","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo-Hyun","family":"Cho","sequence":"additional","affiliation":[{"name":"Robert Wood Johnson Medical School Institute for Neurological Therapeutics, and Department of Neurology, Rutgers Biomedical and Health Sciences, Piscataway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Lee","sequence":"additional","affiliation":[{"name":"Rutgers Institute for Translational Medicine and Science, New Brunswick, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annu","family":"Annu","sequence":"additional","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Centre, Department of Medicine, University of Montreal, Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose H.","family":"Ledo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Young","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon-Seong","family":"Kim","sequence":"additional","affiliation":[{"name":"Robert Wood Johnson Medical School Institute for Neurological Therapeutics, and Department of Neurology, Rutgers Biomedical and Health Sciences, Piscataway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven S.","family":"An","sequence":"additional","affiliation":[{"name":"Rutgers Institute for Translational Medicine and Science, New Brunswick, New Jersey, 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