Liver function and Alzheimer's brain pathologies: A longitudinal study: Liver and Alzheimer's pathologies

J Prev Alzheimers Dis. 2025 Jan;12(1):100012. doi: 10.1016/j.tjpad.2024.100012. Epub 2025 Jan 1.

Abstract

Importance: The neuropathological links underlying the association between changes in liver function and AD have not yet been clearly elucidated.

Objective: We aimed to examine the relationship between liver function markers and longitudinal changes in Alzheimer's disease (AD) core pathologies.

Design: Data from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, a longitudinal cohort study initiated in 2014, were utilized.

Setting: Community and memory clinic setting.

Participants: Three hundred forty-seven older adults.

Main outcome and measures: Participants underwent baseline and 2-year follow-up evaluations, including liver function assessments and various brain imaging techniques, such as amyloid and tau PET, FDG-PET, and MRI). Liver function indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin] were examined as exposure variables.

Results: Higher baseline ALT levels were associated with a greater increase in beta-amyloid deposition over 2 years [β = 0.166, Bonferroni-corrected P (PB) = 0.012], while lower total bilirubin levels were associated with a greater increase in tau deposition over the same period (β = -0.570, PB < 0.001). In contrast, AST alone showed no significant association with changes of AD pathologies.

Conclusions and relevance: The findings suggest a possible link between lower liver function and the accumulation of core AD pathologies in the brain. These results also support the possibility that the liver-brain axis could be a potential target for therapeutic or preventive strategies against AD.

Keywords: Alzheimer's disease; Aβ; alanine aminotransferase; tau; total bilirubin.

MeSH terms

  • Aged
  • Alanine Transaminase / blood
  • Alzheimer Disease* / pathology
  • Alzheimer Disease* / physiopathology
  • Amyloid beta-Peptides / metabolism
  • Aspartate Aminotransferases / blood
  • Aspartate Aminotransferases / metabolism
  • Bilirubin / blood
  • Bilirubin / metabolism
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Brain* / diagnostic imaging
  • Brain* / pathology
  • Female
  • Humans
  • Liver / diagnostic imaging
  • Liver / pathology
  • Liver Function Tests
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Positron-Emission Tomography
  • Republic of Korea / epidemiology
  • tau Proteins / metabolism

Substances

  • Alanine Transaminase
  • tau Proteins
  • Aspartate Aminotransferases
  • Amyloid beta-Peptides
  • Bilirubin
  • Biomarkers