Associations of liver function with plasma biomarkers for Alzheimer's Disease

Neurol Sci. 2024 Jun;45(6):2625-2631. doi: 10.1007/s10072-023-07284-9. Epub 2024 Jan 4.

Abstract

Background: Blood-based biomarkers for Alzheimer's disease (AD) are promising to be used in clinical settings. The liver is an important degradation organ of the body. Whether liver function affects the levels of AD biomarkers needs to be studied.

Objective: To investigate the associations between liver function and the plasma levels of AD biomarkers.

Methods: We conducted an ADNI cohort-based cross-sectional study. Thirteen liver function markers commonly used in clinical settings were analyzed: total protein (TP), albumin (AL), globulin (GL), AL/GL ratio (A/G), total bilirubin (TB), direct bilirubin (DB), indirect bilirubin (IB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and γ-glutamyltransferase (GGT). Liquid chromatography-tandem mass spectrometry was used to detect the plasma Aβ42 and Aβ40 concentrations. Single Molecule array technique was used to measure the plasma p-tau181 and NfL concentrations. We used linear regression models to analyze the associations between liver function markers and the levels of AD plasma biomarkers.

Results: ALP was positively associated with the levels of plasma Aβ42 (β = 0.16, P = 0.018) and Aβ40 (β = 0.21, P = 0.004). LDH was positively associated with the levels of plasma p-tau181 (β = 0.09, P = 0.022). While NfL was correlated with multiple liver function markers, including AL, A/G, ALT, AST/ALT, and LDH.

Conclusion: Liver function was associated with the plasma levels of AD biomarkers. It needs to consider the potential influence of liver function on the reference ranges and the interpretation of results for AD biomarkers before clinical use.

Keywords: Alzheimer’s disease; Cross-sectional study; Liver function; Plasma biomarkers.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / physiopathology
  • Amyloid beta-Peptides* / blood
  • Aspartate Aminotransferases / blood
  • Bilirubin / blood
  • Biomarkers* / blood
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Humans
  • Liver / physiopathology
  • Liver Function Tests
  • Male
  • Neurofilament Proteins / blood
  • Peptide Fragments / blood
  • tau Proteins / blood

Substances

  • Biomarkers
  • Amyloid beta-Peptides
  • tau Proteins
  • Peptide Fragments
  • Alkaline Phosphatase
  • Aspartate Aminotransferases
  • amyloid beta-protein (1-42)
  • amyloid beta-protein (1-40)
  • Alanine Transaminase
  • Bilirubin
  • Neurofilament Proteins