Effects of CD33 Variants on Neuroimaging Biomarkers in Non-Demented Elders

Article type: Research Article

Authors: Wang, Ya-Juan^a | Wan, Yu^b | Wang, Hui-Fu^b | Tan, Chen-Chen^b | Li, Jie-Qiong^b | Yu, Jin-Tai^{a; c; *} | Tan, Lan^{a; b; *} | Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, China | [b] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, China | [c] Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China

Correspondence: [*] Correspondence to: Jin-Tai Yu, Department of Neurology, Huashan Hospital, Fudan University and Lan Tan, Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, No.5 Donghai Middle Road, Qingdao, Shandong Province 266071, China. E-mails: dr.tanlan@163.com (Lan Tan) or yu-jintai@163.com (Jin-Tai Yu).

Note: [1] Data used in preparation for this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://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.

Abstract: Two CD33 common variants, rs3826656 and rs3865444, have been identified to be correlated with Alzheimer’s disease (AD). Our study examined the effects of the two AD-related CD33 common variants (rs3826656 and rs3865444) on the chosen AD-related brain regions (including hippocampus, amygdala, parahippocampus, middle temporal, entorhinal cortex, and total brain volume) in non-demented elders recruited from the Alzheimer’s Disease Neuroimaging Initiative database at baseline and during four-year follow-up. We further tested the effects in an Aβ-positive group (including preclinical and prodromal stage of AD) and an Aβ-negative group. In the total non-demented elderly population, no associations reached significant levels after FDR correction. In the Aβ-positive group, we found that rs3826656 was associated with hippocampal and amygdala volumes (Hippocampus-R: pc = 0.0022; Amygdala-L: pc = 0.0044; Amygdala-R: pc = 0.0066), and rs3865444 was associated with right entorhinal volume (pc = 0.0286). The associations of rs3826656 with hippocampal and amygdala volumes in the Aβ-positive group were successfully replicated in the prodromal AD group (Hippocampus-R: pc = 0.0022; Amygdala-L: pc = 0.0022; Amygdala-R: pc = 0.0088). These changes became more obvious over time during four-year follow-up. No associations were found between the two CD33 variants and neuroimaging biomarkers in the Aβ-negative and preclinical AD groups after FDR correction. These results suggested that the two CD33 common variants (rs3826656 and rs3865444) influenced volumes and atrophy rates of AD-related brain regions in non-demented elders. Subgroup analyses showed the effects mainly existed in the Aβ-positive group instead of the Aβ-negative group, and the effects began in the prodromal AD stage.

Keywords: Alzheimer’s disease, brain structure, CD33, neuroimaging, non-demented elders, polymorphism

DOI: 10.3233/JAD-181062

Journal: Journal of Alzheimer's Disease, vol. 68, no. 2, pp. 757-766, 2019