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Psychiatry"},{"key":"10.1016\/j.tips.2026.07.008_bb0585","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s00401-020-02191-1","article-title":"Reduction of advanced tau-mediated memory deficits by the MAP kinase p38\u03b3","volume":"140","author":"Ittner","year":"2020","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.tips.2026.07.008_bb0590","doi-asserted-by":"crossref","first-page":"6518","DOI":"10.1038\/s41467-026-73207-9","article-title":"Tau T205 phosphorylation modulates engram cell recruitment and remote memory in mice","volume":"17","author":"Kosonen","year":"2026","journal-title":"Nat. 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