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Common Variant in TREM1 Influencing Brain Amyloid Deposition in Mild Cognitive Impairment and Alzheimer’s Disease

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Abstract

Triggering receptor expressed on myeloid cells-1 (TREM1) has been reported to associate with Alzheimer’s disease (AD) pathology. Recently, TREM1 variant rs2234246A was reported to regulate TREM-1 protein and mRNA levels. We explored the effect of rs2234246 on AD specific biomarker (amyloid-β PET) to look into the role of this TREM1 locus in AD pathogenesis. We calculated the association of the TREM1 locus with amyloid deposition at baseline and follow-up using both multiple linear models and mixed effect models respectively in 522 the Alzheimer’s Disease Neuroimaging Initiative (ADNI) subjects. We also analyzed the association of TREM1 with this marker in subregions during the AD process. In the pooled sample, TREM1 rs2234246A was associated with the levels of mean standard uptake volume ratios (SUVRs) at baseline (p = 0.02) and the length of follow-up (p = 0.04) in the cross-sectional analysis and longitudinal study. Subgroup analyses showed no correlation between rs2234246A and amyloid deposition in the cognitively normal (CN) group. In the mild cognitive impairment (MCI) group, TREM1 rs2234246A reached significance at baseline (p = 0.04) and the length of follow-up (p = 0.04). In the AD group, TREM1 rs2234246A was associated with mean SUVR at baseline (p < 0.001) and the length of follow-up (p = 0.001). In subregion analyses, TREM1 rs2234246A was detected to be related to Aβ deposition. This study demonstrated an association between TREM1 variant rs2234246 and brain amyloidosis. Our findings implied that this variant is involved in AD by influencing Aβ neuropathology.

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Data Availability

Data used in preparation for 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/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

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Funding

This study was supported by grants from the National Natural Science Foundation of China (81771148, 91849126), the National Key R&D Program of China (2018YFC1314700), Shanghai Municipal Science and Technology Major Project (No.2018SHZDZX01) and ZHANGJIANG LAB, Tianqiao and Chrissy Chen Institute, and the State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University. Data acquisition 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). Funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering, ADNI also gets substantial donations from the following institutions: 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 give finical support to the ADNI clinical sites in Canada. Private sector fund raising is facilitated by the Foundation for the National Institutes of Health (www.fnih.org). For this study, the grantee organization is the Northern California Institute for Research and Education, and the coordinator is the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are spread by the Laboratory for Neuro Imaging at the University of Southern California.

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  1. Yue-Song Liu and Wen-Jing Yan contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, No. 5 Donghai Middle Road, Qingdao, China

    Yue-Song Liu & Lan Tan

  2. Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China

    Wen-Jing Yan

  3. Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Sheng, China

    Chen-Chen Tan, Jie-Qiong Li & Wei Xu

  4. Clinical Research Center, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Sheng, China

    Xi-Peng Cao

  5. Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12 Wulumuqi Road, Shanghai, China

    Jin-Tai Yu

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  1. Yue-Song Liu
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Alzheimer’s Disease Neuroimaging Initiative

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Correspondence to Lan Tan or Jin-Tai Yu.

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Liu, YS., Yan, WJ., Tan, CC. et al. Common Variant in TREM1 Influencing Brain Amyloid Deposition in Mild Cognitive Impairment and Alzheimer’s Disease. Neurotox Res 37, 661–668 (2020). https://doi.org/10.1007/s12640-019-00105-y

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