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

Galit Weinstein, Adrienne O'Donnell, Kendra Davis-Plourde, Shira Zelber-Sagi, Saptaparni Ghosh, Charles S. Decarli, Emma G. Thibault, Reisa A. Sperling, Keith A. Johnson, Alexa S. Beiser, Sudha Seshadri

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1371-1383
Number of pages13
JournalJournal of Alzheimer's Disease
Volume86
Issue number3
DOIs
StatePublished - 2022

Bibliographical note

Funding Information:
This study was supported by grants from the National Institute on Aging (R01 AG054076, R01 AG049607, R01 AG033040, R01 AG063507, U01 AG052409, RF1 AG061872, U01 AG049505, U01 AG058589, and P30 AG066546), the National Institute of Neurological Disorders and Stroke (R01 NS017950 and UH2 NS100605), and the NHLBI contract for the Framingham Heart Study (contract no. N01-HC-25195, HHSN268201500001I, and 75N92019D00031).

Funding Information:
This study was supported by grants from the National Institute on Aging (R01 AG054076, R01 AG049607, R01 AG033040, R01 AG063507, U01 AG052409, RF1 AG061872, U01 AG049505, U01 AG058589, and P30 AG066546), the National Institute of Neurological Disorders and Stroke (R01

Publisher Copyright:
© 2022 - IOS Press. All rights reserved.

Keywords

  • Alzheimer's disease
  • amyloid-β
  • liver fibrosis
  • non-alcoholic fatty liver disease
  • positron emission tomography

ASJC Scopus subject areas

  • Neuroscience (all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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