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

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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.

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Data availability

The data used in this study are openly available on the ADNI website at www.adni-info.org.

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Acknowledgements

Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, Araclon Biotech, BioClinica, Inc., Biogen, BristolMyers Squibb Company, CereSpir, Inc., Cogstate; Eisai Inc., Elan Pharmaceuticals, Inc., Eli Lilly and Company, EuroImmun, F.Hoffmann-La Roche Ltd., and its affiliated company Genentech, Inc., Fujirebio, GE Healthcare, IXICO Ltd., Janssen Alzheimer Immunotherapy Research and Development, LLC., Johnson & Johnson Pharmaceutical Research and Development, LLC., Lumosity, Lundbeck; Merck & Co., Inc., Meso Scale Diagnostics, LLC., NeuroRx Research, Neurotrack Technologies, Novartis Pharmaceuticals Corporation, Pfizer Inc., Piramal Imaging, Servier, Takeda Pharmaceutical Company, and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuroimaging at the University of Southern California.

Funding

This work was supported by the National Key R&D Program of China (Grant No. 2022YFC2010103) and the Central health research project (Grant No. 2020ZD10).

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Author notes

  1. Bin Zhang and Cheng Zhang these authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Bin Zhang, YuYe Wang, LeiAn Cheng & Dantao Peng

  2. International Acupuncture and Moxibustion Innovation Institute, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China

    Cheng Zhang

  3. Department of Neurology, China-Japan Friendship Hospital, Beijing, China

    Yu Wang & YaNan Qiao

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  1. Bin Zhang
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for the Alzheimer’s Disease Neuroimaging Initiative

Contributions

Bin Zhang: study design, analysis of data, and manuscript drafting. Cheng Zhang: study design and statistical analysis. Yu YeWang and Lei AnChen: revision of manuscript. Ya NanQiao, YuWang and Dang TaoPeng: study design and revision of manuscript. All authors reviewed and approved the final version of the manuscript.

Corresponding authors

Correspondence to YaNan Qiao or Dantao Peng.

Ethics declarations

Ethical approval

All data used in the study was from the ADNI cohort. The ADNI cohort was authorized by the local institutional review committee and conducted in accordance with the Declaration of Helsinki.

Informed consent

Informed consent was obtained from all subjects involved in the ADNI cohort.

Conflict of interest

The authors declare no competing interests.

Disclaimer

The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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Data used in the preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wpcontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

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Zhang, B., Zhang, C., Wang, Y. et al. Associations of liver function with plasma biomarkers for Alzheimer’s Disease. Neurol Sci 45, 2625–2631 (2024). https://doi.org/10.1007/s10072-023-07284-9

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