{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T03:20:37Z","timestamp":1791602437533,"version":"4.3.4"},"posted":{"date-parts":[[2025,6,20]]},"group-title":"Neuroscience","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,20]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Tau aggregates propagate through the brain in a prion-like manner in Alzheimer\u2019s disease (AD) and other tauopathies, but the molecular identity and functional partners of the seeding-competent Tau species remain poorly defined. Here, we present an unbiased proteomic profiling of a high-molecular-weight (HMW) Tau-seed isolated from AD patient brains. We contrast this interactome with that of a biochemically similar, seeding-incompetent HMW-Tau species from age-matched healthy controls. Despite comprising less than 5% of total Tau in the brain, Tau-seed associates with a distinct set of proteins enriched in synaptic, mitochondrial, and vesicle-trafficking functions. Cross-species functional screening in\n                  <jats:italic>Drosophila<\/jats:italic>\n                  and mouse models identifies interactors that modulate Tau toxicity and seeding. Spatially resolved analysis of postmortem AD brains reveals heterogenous co-deposition of these proteins with Tau aggregates, suggesting functionally distinct Tau-seed complexes. Together, this dataset provides a framework for understanding selective Tau-seed toxicity and identifies candidate regulators of Tau propagation with therapeutic potential.\n                <\/jats:p>","DOI":"10.1101\/2025.06.17.660179","type":"posted-content","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T12:15:19Z","timestamp":1750421719000},"source":"Crossref","is-referenced-by-count":1,"title":["Tau-seed interactome analysis reveals distinct functional signatures in Alzheimer\u2019s disease across model systems"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3496-4652","authenticated-orcid":false,"given":"Pablo","family":"Martinez","sequence":"first","affiliation":[{"name":"Department of Neurology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2654-4669","authenticated-orcid":false,"given":"Henika","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Neurology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwen","family":"You","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniella","family":"Lopes","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Amaro","sequence":"additional","affiliation":[{"name":"Department of Neurology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1143-3595","authenticated-orcid":false,"given":"Nur","family":"Jury-Garfe","sequence":"additional","affiliation":[{"name":"Department of Neurology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Redding-Ochoa","sequence":"additional","affiliation":[{"name":"Division of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3577-2193","authenticated-orcid":false,"given":"Sayan","family":"Dutta","sequence":"additional","affiliation":[{"name":"Purdue Inst. for Integrative Neuroscience, Purdue University, Lafayette, IN, USA"},{"name":"Dep. of Medicinal Chemistry and Molecular Pharmacology, Purdue University, Lafayette, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Rochet","sequence":"additional","affiliation":[{"name":"Purdue Inst. for Integrative Neuroscience, Purdue University, Lafayette, IN, USA"},{"name":"Dep. of Medicinal Chemistry and Molecular Pharmacology, Purdue University, Lafayette, IN, 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