Non-Alcoholic Fatty Liver Disease, Liver Fibrosis, and Regional Amyloid-β and Tau Pathology in Middle-Aged Adults: The Framingham Study

  • Galit Weinstein
    School of Public Health, University of Haifa, Haifa, Israel
  • Adrienne O’Donnell
    Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
  • Kendra Davis-Plourde
    Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
  • Shira Zelber-Sagi
    School of Public Health, University of Haifa, Haifa, Israel
  • Saptaparni Ghosh
    The Framingham Study, Framingham, MA, USA
  • Charles S. DeCarli
    Department of Neurology, School of Medicine & Imaging of Dementia and Aging Laboratory, Center for Neuroscience, University of California Davis, Davis, CA, USA
  • Emma G. Thibault
    Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  • Reisa A. Sperling
    Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  • Keith A. Johnson
    Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  • Alexa S. Beiser
    Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
  • Sudha Seshadri
    The Framingham Study, Framingham, MA, USA

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<jats:p>Background: Liver steatosis and fibrosis are emerging as risk factors for multiple extrahepatic health conditions; however, their relationship with Alzheimer’s 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-β (Aβ) and tau pathology. Methods: The study sample included Framingham Study participants from the Offspring and Third generation cohorts who attended exams 9 (2011–2014) and 2 (2008–2011), 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 Aβ, adjusting for potential confounders and multiple comparisons. Results: Of the subsample with NAFLD information (N = 169; mean age 52±9 y; 57% males), 57 (34%) had NAFLD. Of the subsample with information on liver fibrosis (N = 177; mean age 50±10 y; 51% males), 34 (19%) had advanced fibrosis (FIB-4 > 1.3). Prevalent NAFLD was not associated with Aβ or tau PET. However, FIB-4 index was significantly associated with increased rhinal tau (β= 1.03±0.33, p = 0.002). Among individuals with prevalent NAFLD, FIB-4 was related to inferior temporal, parahippocampal gyrus, entorhinal and rhinal tau (β= 2.01±0.47, p < 0.001; β= 1.60±0.53, p = 0.007, and β= 1.59±0.47, p = 0.003 and β= 1.60±0.42, p = 0.001, respectively) and to Aβ deposition overall and in the inferior temporal and parahippocampal regions (β= 1.93±0.47, p < 0.001; β= 1.59±0.38, p < 0.001, and β= 1.52±0.54, p = 0.008, respectively). Conclusion: This study suggests a possible association between liver fibrosis and early Alzheimer’s disease pathology, independently of cardio-metabolic risk factors.</jats:p>

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