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Epilepsy and AD are linked but the shared pathophysiological changes remain poorly defined. We aim to identify protein differences associated with epilepsy and AD using published proteomics datasets. We observed a highly significant overlap in protein differences in epilepsy and AD: 89% (689\/777) of proteins altered in the hippocampus of epilepsy patients were significantly altered in advanced AD. Of the proteins altered in both epilepsy and AD, 340 were altered in the same direction, while 216 proteins were altered in the opposite direction. Synapse and mitochondrial proteins were markedly decreased in epilepsy and AD, suggesting common disease mechanisms. In contrast, ribosome proteins were increased in epilepsy but decreased in AD. Notably, many of the proteins altered in epilepsy interact with tau or are regulated by tau expression. This suggests that tau likely mediates common protein changes in epilepsy and AD. Immunohistochemistry for A\u03b2 and multiple phosphorylated tau species (pTau396\/404, pTau217, pTau231) showed a trend for increased intraneuronal pTau217 and pTau231 but no phosphorylated tau aggregates or amyloid plaques in epilepsy hippocampal sections. Our results provide insights into common mechanisms in epilepsy and AD and highlights the potential role of tau in mediating common pathological protein changes in epilepsy and AD.<\/jats:p>","DOI":"10.1007\/s00401-024-02683-4","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T11:02:05Z","timestamp":1706612525000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Similar brain proteomic signatures in Alzheimer\u2019s disease and epilepsy"],"prefix":"10.1007","volume":"147","author":[{"given":"Dominique","family":"Leitner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"Pires","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Kavanagh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny","family":"Kanshin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manor","family":"Askenazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrix","family":"Ueberheide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orrin","family":"Devinsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Wisniewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5466-4609","authenticated-orcid":false,"given":"Eleanor","family":"Drummond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,30]]},"reference":[{"key":"2683_CR1","doi-asserted-by":"publisher","first-page":"4466","DOI":"10.1038\/s41467-023-40208-x","volume":"14","author":"M Askenazi","year":"2023","unstructured":"Askenazi M, Kavanagh T, Pires G, Ueberheide B, Wisniewski T, Drummond E (2023) Compilation of reported protein changes in the brain in Alzheimer\u2019s disease. 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