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

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-beta (A beta) 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 C-11-Pittsburgh Compound-B amyloid and F-18-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 beta, 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 A beta or tau PET. However, FIB-4 index was significantly associated with increased rhinal tau (beta = 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 (beta = 2.01 +/- 0.47, p < 0.001; beta = 1.60 +/- 0.53, p = 0.007, and beta = 1.59 +/- 0.47, p = 0.003 and beta = 1.60 +/- 0.42, p = 0.001, respectively) and to A beta deposition overall and in the inferior temporal and parahippocampal regions (beta = 1.93 +/- 0.47, p < 0.001; beta = 1.59 +/- 0.38, p < 0.001, and beta = 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. Conclusion: This study suggests a possible association between liver fibrosis and early Alzheimer's disease pathology, independently of cardio-metabolic risk factors.

Automated summary

This study suggests a possible association between liver fibrosis and early Alzheimer's disease pathology, independently of cardio-metabolic risk factors.