Liver function and Alzheimer's brain pathologies: A longitudinal study : Liver and Alzheimer's pathologies - 02/01/25

Doi : 10.1016/j.tjpad.2024.100012

Jee Wook Kim ^a,^b , Min Soo Byun ^c,^d , Dahyun Yi ^e , Joon Hyung Jung ^f , Nayeong Kong ^g , Yoon Young Chang ^h , Gijung Jung ^c , Hyejin Ahn ⁱ , Jun-Young Lee ^d,^j , Koung Mi Kang ^k , Chul-Ho Sohn ^k , Yun-Sang Lee ^l , Yu Kyeong Kim ^m , Dong Young Lee ^c,^d,^e,^i,^⁎
for the
for the KBASE Research Group¹
Membership of the KBASE Research Group are listed in elsewhere (kbase.kr).
^a Department of Neuropsychiatry, Hallym University Dongtan Sacred Heart Hospital, 7 Keunjaebong-gil, Hwaseong, Gyeonggi, 18450, Republic of Korea
^b Department of Psychiatry, Hallym University College of Medicine, Chuncheon, Gangwon, 24252, Republic of Korea
^c Department of Neuropsychiatry, Seoul National University Hospital, Seoul, 03080, Republic of Korea
^d Department of Psychiatry, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
^e Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, 03080, Republic of Korea
^f Department of Psychiatry, Chungbuk National University Hospital, Cheongju, 28644, Republic of Korea
^g Department of Psychiatry, Keimyung University Dongsan Hospital, Daegu, 42601, Republic of Korea
^h Department of Psychiatry, Inje University Sanggye Paik Hospital, Seoul, 01757, Republic of Korea
ⁱ Interdisciplinary Program of Cognitive Science, Seoul National University College of Humanities, Seoul, 08826, Republic of Korea
^j Department of Neuropsychiatry, SMG-SNU Boramae Medical Center, Seoul, 07061, Republic of Korea
^k Department of Radiology, Seoul National University Hospital, Seoul, 03080, Republic of Korea
^l Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
^m Department of Nuclear Medicine, SMG-SNU Boramae Medical Center, Seoul, 07061, Republic of Korea

^⁎Corresponding author at: Department of Neuropsychiatry, Seoul National University Hospital & Department of Psychiatry, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.Department of NeuropsychiatrySeoul National University HospitalDepartment of PsychiatrySeoul National University College of Medicine101 Daehak-ro, Jongno-guSeoul03080Republic of Korea

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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 (P_B) = 0.012], while lower total bilirubin levels were associated with a greater increase in tau deposition over the same period (β = -0.570, P_B < 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.

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