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AST/ALT, <i>APOE</i> ε4, and Alzheimer's disease progression: A longitudinal cohort study.

Overview

Authors: Young Hyeon Ahn1, Chan‐Mo Yang2,3, Dae‐Jin Kim3, Sae Hwan Lee1, Young Hyun Jung4,5, Sang‐Yeol Lee2,3, Sung‐Hoon Yoon2,3, for the Alzheimer's Disease Neuroimaging Initiative
ORCID iDs: Sung‐Hoon Yoon
  1. Department of Gastroenterology, Soonchunhyang University Cheonan Hospital, Cheonan, South Korea
  2. Department of Psychiatry, Wonkwang University Hospital, Iksan, South Korea
  3. Department of Psychiatry, School of Medicine, Wonkwang University, Iksan, South Korea
  4. Department of Physiology, College of Medicine, Soonchunhyang University, Cheonan, South Korea
  5. Institute for Molecular Metabolism Innovation, Soonchunhyang University, Asan, Republic of Korea
Institutions: Soonchunhyang University (South Korea); Soonchunhyang University Hospital Cheonan (South Korea); Wonkwang University Hospital (South Korea); Wonkwang University (South Korea)
Journal: Alzheimer's & dementia (Amsterdam, Netherlands), volume 18, issue 3, article e70484
Dates: received 16 June 2026; accepted 17 August 2026; published online 13 September 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1002/dad2.70484 · PMID 42741023 · PMCID PMC13572572 · OpenAlex W7212436867
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: human (organism), Alzheimer's / dementia (population), clinical / translational (subfield)
Methods: Connectivity, Statistics, fMRI & imaging, Preprocessing
Keywords: alzheimer's disease, alzheimer's Disease Neuroimaging Initiative, apolipoprotein E ε4, aspartate aminotransferase‐to‐alanine aminotransferase ratio, biomarkers, clinical progression, cognitive decline, cortical thinning, liver‐enzyme markers, longitudinal
Topic: Dementia and Cognitive Impairment Research (Psychiatry and Mental health, Medicine), according to OpenAlex
Funding: NIA NIH HHS (U19 AG024904)
Citations: not cited yet (Europe PMC); 48 references in the paper

Abstract

INTRODUCTION: The aspartate aminotransferase‐to‐alanine aminotransferase (AST/ALT) ratio is a routinely available liver‐enzyme index. Whether apolipoprotein E (APOE) ε4 modifies associations of baseline AST/ALT with longitudinal Alzheimer's disease (AD) trajectories is unclear.

METHODS: In 2709 Alzheimer's Disease Neuroimaging Initiative participants, linear mixed‐effects models estimated AST/ALT‐associated longitudinal change in Mini‐Mental State Examination, Alzheimer's Disease Assessment Scale 13‐item Cognitive subscale, and AD‐signature cortical thickness; Cox models evaluated continuous AST/ALT and an extreme‐tertile APOE ε4 × AST/ALT comparison for clinical progression.

RESULTS: Higher baseline AST/ALT was associated with faster cognitive decline and AD‐signature cortical thinning, with larger associations among APOE ε4 carriers (interaction p = .0006–0.040). In clinical‐progression analyses, continuous AST/ALT was not significantly associated with risk (hazard ratio [HR] 1.07 per standard deviation, p = 0.12). In the extreme‐tertile comparison, APOE ε4 carriers with high AST/ALT had the highest adjusted hazard (HR 3.08, 95% confidence interval 2.18–4.34), but multiplicative and additive interactions were null and incremental discrimination was minimal (ΔC = +0.003).

DISCUSSION: Baseline AST/ALT was associated with faster cognitive and cortical decline, particularly among APOE ε4 carriers, but provided limited incremental information for clinical progression beyond APOE ε4 and baseline diagnosis. These findings represent a large longitudinal extension of prior liver‐enzyme observations and require external validation.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

No dataset and no data link were found in the paper.

Data availability statement

The data analyzed in this study are publicly available through the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu) under the ADNI Data Use Agreement. Analytic code used in this study is available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 10 keywords, 1 funder, 48 references.

Cite

This paper

Ahn, Y. H., Yang, C., Kim, D., Lee, S. H., Jung, Y. H., Lee, S., Yoon, S., & for the Alzheimer's Disease Neuroimaging Initiative. (2026). AST/ALT, <i>APOE</i> ε4, and Alzheimer's disease progression: A longitudinal cohort study. Alzheimer's & dementia (Amsterdam, Netherlands), 18(3), e70484. https://doi.org/10.1002/dad2.70484

BibTeX

@article{ahn2026ast,
author = {Ahn, Young Hyeon and Yang, Chan‐Mo and Kim, Dae‐Jin and Lee, Sae Hwan and Jung, Young Hyun and Lee, Sang‐Yeol and Yoon, Sung‐Hoon and {for the Alzheimer's Disease Neuroimaging Initiative}},
title = {{AST/ALT, \<i\>APOE\</i\> ε4, and Alzheimer's disease progression: A longitudinal cohort study}},
journal = {Alzheimer's \& dementia (Amsterdam, Netherlands)},
year = {2026},
month = jul,
volume = {18},
number = {3},
pages = {e70484},
publisher = {Wiley},
issn = {2352-8729},
doi = {10.1002/dad2.70484},
url = {https://doi.org/10.1002/dad2.70484},
pmid = {42741023},
pmcid = {PMC13572572}
}

RIS

TY - JOUR
AU - Ahn, Young Hyeon
AU - Yang, Chan‐Mo
AU - Kim, Dae‐Jin
AU - Lee, Sae Hwan
AU - Jung, Young Hyun
AU - Lee, Sang‐Yeol
AU - Yoon, Sung‐Hoon
AU - for the Alzheimer's Disease Neuroimaging Initiative
TI - AST/ALT, <i>APOE</i> ε4, and Alzheimer's disease progression: A longitudinal cohort study
T2 - Alzheimer's & dementia (Amsterdam, Netherlands)
J2 - Alzheimers Dement (Amst)
PY - 2026
DA - 2026/07/01
VL - 18
IS - 3
SP - e70484
SN - 2352-8729
PB - Wiley
DO - 10.1002/dad2.70484
UR - https://doi.org/10.1002/dad2.70484
LA - en
ER -

CSL-JSON

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