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Association of APOE gene with longitudinal changes of CSF amyloid beta and tau levels in Alzheimer’s disease: racial differences

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Abstract

Background

The Apolipoprotein E (APOE) ε4 allele is a risk factor for late-onset Alzheimer’s disease (AD). However, no investigation has focused on racial differences in the longitudinal effect of APOE genotypes on CSF amyloid beta (Aβ42) and tau levels in AD.

Methods

This study used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI): 222 participants with AD, 264 with cognitive normal (CN), and 692 with mild cognitive impairment (MCI) at baseline and two years follow-up. We used a linear mixed model to investigate the effect of APOE-ε4-genotypes on longitudinal changes in the amyloid beta and tau levels.

Results

Individuals with 1 or 2 APOE ε4 alleles revealed significantly higher t-Tau and p-Tau, but lower amyloid beta Aβ42 compared with individuals without APOE ε4 alleles. Significantly higher levels of log-t-Tau, log-p-Tau, and low levels of log-Aβ42 were observed in the subjects with older age, being female, and the two diagnostic groups (AD and MCI). The higher p-Tau and Aβ42 values are associated with poor Mini-Mental State Examination (MMSE) performance. Non-Hispanic Africa American (AA) and Hispanic participants were associated with decreased log-t-Tau levels (β =  − 0.154, p = 0.0112; β =  − 0.207, and p = 0.0016, respectively) as compared to those observed in Whites. Furthermore, Hispanic participants were associated with a decreased log-p-Tau level (β =  − 0.224, p = 0.0023) compared to those observed in Whites. There were no differences in Aβ42 level for non-Hispanic AA and Hispanic participants compared with White participants.

Conclusion

Our study, for the first time, showed that the APOE ε4 allele was associated with these biomarkers, however with differing degrees among racial groups.

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Data availability

Data used in the preparation of this article was obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu).

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Acknowledgements

The present study is a secondary data analysis. The original study and ADNI were 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, the 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; Bristol-Myers 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 & Development, LLC.; Johnson & Johnson Pharmaceutical Research & 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 Neuro Imaging at the University of Southern California. Data used in 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 analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

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Authors and Affiliations

  1. Department of Health and Biomedical Sciences, College of Health Professions, University of Texas Rio Grande Valley, Brownsville, TX, 78520, USA

    Chun Xu, Jaime Miguel Saveron, Daniela Gamez & Upal Roy

  2. Department of STEM, School of Arts and Sciences, Regis College, Weston, MA, 02493, USA

    Danqing Xiao

  3. Department of Pediatrics – Allergy and Immunology, Baylor College of Medicine, Houston, TX, 77030, USA

    Brenda Bin Su

  4. Department of Medicine and Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, 26506, USA

    R. Osvaldo Navia

  5. Department of Health Policy and Management, School of Public Health, University of Maryland, College Park, MD, 20742, USA

    Nianyang Wang

  6. Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, WV, 26506, USA

    Donald A. Adjeroh

  7. Department of Family and Community Health, School of Nursing, Health Sciences Center, West Virginia University, Morgantown, WV, 26506, USA

    Kesheng Wang

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  1. Chun Xu
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The Alzheimer and Disease Neuroimaging Initiative

Contributions

Conceptualization, C.X. and K.W.; methodology, C.X., D.X., B.B.S., and K.W.; data analysis and interpretation, C.X., D.X., N.W., D.A.A., and K.W.; investigation, C.X., D.X., and K.W.; writing—original draft preparation, C.X., D.X., J.M.S., D.G., U.R., and K.W.; writing—review and editing, D.X., B.B.S., O.R.N., N.W., and D.A.A.; supervision, C.X. and K.W.; all authors read and agreed to the published version of the manuscript. The Alzheimer’s Disease Neuroimaging Initiative—data used in the preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu).

Corresponding author

Correspondence to Kesheng Wang.

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Ethical approval

There was an Institutional Review Board exemption for the current study due to secondary data analysis. Data used in the preparation of this article was obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu).

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Informed consent was obtained from all subjects involved in the original study. Data used in the preparation of this article was obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu).

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Xu, C., Xiao, D., Su, B.B. et al. Association of APOE gene with longitudinal changes of CSF amyloid beta and tau levels in Alzheimer’s disease: racial differences. Neurol Sci 45, 1041–1050 (2024). https://doi.org/10.1007/s10072-023-07076-1

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