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However, it is unknown what is the impact of the AD risk factors, personality characteristics assessed by the NEO Five-Factor Inventory, on the human brain\u2019s transcriptome. Using postmortem human brain samples from 466 subjects, we found that neuroticism has a significant overall impact on the brain transcriptome (omnibus\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.005) but not the other four personality characteristics. Focused on those cognitive decline related gene co-expressed modules, neuroticism has nominally significant associations (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05) with four neuronal modules, which are more related to PHFtau than A\u03b2 across all eight brain regions. Furthermore, the effect of neuroticism on cognitive decline and AD might be mediated through the expression of module 7 and TAU pathology (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.008). To conclude, neuroticism has a broad impact on the transcriptome of human brains, and its effect on cognitive decline and AD may be mediated through gene transcription programs related to TAU pathology.\n                  <\/jats:p>","DOI":"10.1038\/s41398-021-01253-6","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T09:18:43Z","timestamp":1614158323000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Neuroticism alters the transcriptome of the frontal cortex to contribute to the cognitive decline and onset of Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"11","author":[{"given":"C\u00e9line H.","family":"De Jager","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles C.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3609-8877","authenticated-orcid":false,"given":"Yiyi","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"1253_CR1","doi-asserted-by":"publisher","first-page":"5243","DOI":"10.1007\/s12035-017-0757-2","volume":"55","author":"V Theendakara","year":"2018","unstructured":"Theendakara, V., Peters-Libeu, C. 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