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In particular, the impacts of tau mutations, phosphorylation and aggregation on axonal transport in vivo remain controversial. By using two-photon imaging of axonal transport of BDNF granules in the mouse cortex, we reveal that deficits in axonal transport arise in vivo at early stages of tau pathology, preceding tangle formation and neuronal death. Mechanistically, these impairments are caused by the enlargement of tau envelopes on microtubules, which act as functional barriers for transport. Crucially, these deficits are reversed by inhibiting MAPK p38\u03b1. Together, our work demonstrates that tau pathology causes reversible deficits in axonal transport in vivo, posing the basis for pharmacological interventions to restore the physiological flux of axonal organelles and cargoes in tauopathies.<\/jats:p>","DOI":"10.1038\/s41593-026-02266-4","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T09:03:47Z","timestamp":1780563827000},"page":"1355-1368","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Aberrant tau accumulation caused by MAPT mutations induces early pathological changes in axonal transport that are rescued by p38\u03b1 inhibition"],"prefix":"10.1038","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3546-6797","authenticated-orcid":false,"given":"Edoardo","family":"Moretto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Masato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1169-7870","authenticated-orcid":false,"given":"Chiara","family":"Panzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 T.","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Skye","family":"Stuart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"De La-Rocque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Giuseppa","family":"Caso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian J.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel S.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4416-7553","authenticated-orcid":false,"given":"Marc Aurel","family":"Busche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4319-8745","authenticated-orcid":false,"given":"Giampietro","family":"Schiavo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"2266_CR1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/nrn.2015.1","volume":"17","author":"Y Wang","year":"2016","unstructured":"Wang, Y. & Mandelkow, E. 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