{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:14:50Z","timestamp":1788311690945,"version":"build-2803163510"},"reference-count":82,"publisher":"SAGE Publications","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,4,5]]},"abstract":"<jats:p>Background: Liver steatosis and fibrosis are emerging as risk factors for multiple extrahepatic health conditions; however, their relationship with Alzheimer\u2019s disease pathology is unclear. Objective: To examine whether non-alcoholic fatty liver disease (NAFLD) and FIB-4, a non-invasive index of advanced fibrosis, are associated with brain amyloid-\u03b2 (A\u03b2) and tau pathology. Methods: The study sample included Framingham Study participants from the Offspring and Third generation cohorts who attended exams 9 (2011\u20132014) and 2 (2008\u20132011), respectively. Participants underwent 11C-Pittsburgh Compound-B amyloid and 18F-Flortaucipir tau positron emission tomography (PET) imaging and abdomen computed tomography, or had information on all components of the FIB-4 index. Linear regression models were used to assess the relationship of NAFLD and FIB-4 with regional tau and A\u03b2, adjusting for potential confounders and multiple comparisons. Results: Of the subsample with NAFLD information (N\u200a=\u200a169; mean age 52\u00b19\u200ay; 57% males), 57 (34%) had NAFLD. Of the subsample with information on liver fibrosis (N\u200a=\u200a177; mean age 50\u00b110\u200ay; 51% males), 34 (19%) had advanced fibrosis (FIB-4\u200a&gt;\u200a1.3). Prevalent NAFLD was not associated with A\u03b2 or tau PET. However, FIB-4 index was significantly associated with increased rhinal tau (\u03b2=\u200a1.03\u00b10.33, p\u200a=\u200a0.002). Among individuals with prevalent NAFLD, FIB-4 was related to inferior temporal, parahippocampal gyrus, entorhinal and rhinal tau (\u03b2=\u200a2.01\u00b10.47, p\u200a&lt;\u200a0.001; \u03b2=\u200a1.60\u00b10.53, p\u200a=\u200a0.007, and \u03b2=\u200a1.59\u00b10.47, p\u200a=\u200a0.003 and \u03b2=\u200a1.60\u00b10.42, p\u200a=\u200a0.001, respectively) and to A\u03b2 deposition overall and in the inferior temporal and parahippocampal regions (\u03b2=\u200a1.93\u00b10.47, p\u200a&lt;\u200a0.001; \u03b2=\u200a1.59\u00b10.38, p\u200a&lt;\u200a0.001, and \u03b2=\u200a1.52\u00b10.54, p\u200a=\u200a0.008, respectively). Conclusion: This study suggests a possible association between liver fibrosis and early Alzheimer\u2019s disease pathology, independently of cardio-metabolic risk factors.<\/jats:p>","DOI":"10.3233\/jad-215409","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T13:23:44Z","timestamp":1645536224000},"page":"1371-1383","source":"Crossref","is-referenced-by-count":49,"title":["Non-Alcoholic Fatty Liver Disease, Liver Fibrosis, and Regional Amyloid-\u03b2 and Tau Pathology in Middle-Aged Adults: The Framingham Study"],"prefix":"10.1177","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1316-4448","authenticated-orcid":false,"given":"Galit","family":"Weinstein","sequence":"first","affiliation":[{"name":"School of Public Health, University of Haifa, Haifa, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA"},{"name":"The Framingham Study, Framingham, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendra","family":"Davis-Plourde","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA"},{"name":"The Framingham Study, Framingham, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shira","family":"Zelber-Sagi","sequence":"additional","affiliation":[{"name":"School of Public Health, University of Haifa, Haifa, Israel"},{"name":"Liver Unit, Department of Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saptaparni","family":"Ghosh","sequence":"additional","affiliation":[{"name":"The Framingham Study, Framingham, MA, USA"},{"name":"Department of Neurology, Boston University School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles S.","family":"DeCarli","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine & Imaging of Dementia and Aging Laboratory, Center for Neuroscience, University of California Davis, Davis, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma G.","family":"Thibault","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reisa A.","family":"Sperling","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa S.","family":"Beiser","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA"},{"name":"The Framingham Study, Framingham, MA, USA"},{"name":"Department of Neurology, Boston University School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudha","family":"Seshadri","sequence":"additional","affiliation":[{"name":"The Framingham Study, Framingham, MA, USA"},{"name":"Department of Neurology, Boston University School of Medicine, Boston, MA, USA"},{"name":"Glenn Biggs Institute for Alzheimer\u2019s and Neurodegenerative Diseases, University of Texas Health Sciences Center, San 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