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Here we assessed postmortem tissue samples from the brains and livers of 100 subjects with ages at death ranging from 51 to 93. Twenty percent of these subjects were demented. We used standardized assessment strategies to assess both the brain and liver pathologies (LP). Our cohort included subjects with none, mild, moderate, and severe LP caused by alcohol consumption. We noted a significant negative correlation of categorical data between liver steatosis and \u03b1-synuclein (\u03b1S) in the brain and a significant negative correlation between the extent of liver steatosis and fibrosis and the extent of \u03b1S in the brain. There was a significant negative association between the observation of Alzheimer\u2019s type II astrocytes and \u03b1S pathology in the brain. No association was noted between LP and hyperphosphorylated \u03c4 (HP\u03c4). No significant correlation could be seen between the extent of LP and the extent of HP\u03c4, amyloid \u03b2 protein (A\u03b2) or transactive DNA binding protein 43 (TDP43) in the brain. There were significant correlations observed between the extent of HP\u03c4, A\u03b2, \u03b1S, and TDP43 in the brain and between liver steatosis, inflammation, and fibrosis. Subjects with severe LP displayed a higher frequency of Alzheimer\u2019s type II astrocytes compared to those with no, or mild, LP. The assessed protein alterations were not more prevalent or severe in subjects with Alzheimer\u2019s type II astrocytes in the brain. In all cases, dementia was attributed to a combination of altered proteins, i.e., mixed dementia and dementia was observed in 30% of those with mild LP when compared with 13% of those with severe LP. In summary, our results are in line with the outcome obtained by the two recent meta-analyses suggesting that subjects with a history of alcohol consumption seldom develop an \u03b1-synucleinopathy.<\/jats:p>","DOI":"10.1007\/s00401-024-02772-4","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T02:02:43Z","timestamp":1722477763000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Alcohol consumers with liver pathology rarely display \u03b1-synuclein pathology"],"prefix":"10.1007","volume":"148","author":[{"given":"Sylwia","family":"Libard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Tamsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6249-569X","authenticated-orcid":false,"given":"Irina","family":"Alafuzoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,1]]},"reference":[{"key":"2772_CR1","doi-asserted-by":"publisher","first-page":"2786","DOI":"10.1002\/jnr.22091","volume":"87","author":"L Aho","year":"2009","unstructured":"Aho L, Karkola K, Juusela J, Alafuzoff I (2009) Heavy alcohol consumption and neuropathological lesions: a post-mortem human study. 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