Affiliations: [a] Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao, China
| [b] Department of Medicine, Hangzhou Juno Genomics Inc, Hangzhou, China
Correspondence:
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Correspondence to: Prof. Song Chi, Department of Neurology, the Affiliated Hospital of Qingdao University, No 16 Jiang Su Road, Qingdao, Shandong 266003, China. Tel.: +86 18661807303; E-mail: qyfyneurology@163.com.
Note: [1] Data used in preparation of 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 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: Background:CC-chemokine ligand 2 (CCL2), the key immunomodulatory chemokine for microglial activation, has been implicated in the pathogenesis of Alzheimer’s disease (AD). Whether the association of CCL2 single nucleotide polymorphisms (SNPs) and the risk of AD is still controversial. Objective:We aimed to investigate whether CCL2 rs4586 SNP is associated with the pathological changes and cognitive decline of AD. Methods:A total of 486 participants with longitudinal cerebrospinal fluid (CSF) amyloid-β (Aβ) and phospho-tau (P-tau) biomarkers, 18F-Florbetapir and 18F-flortaucipir-positron emission tomography (PET), and cognitive assessments from the Alzheimer’s disease Neuroimaging Initiative were included in the study. The effects of CCL2 rs4586 SNP on the pathological changes and cognitive decline of AD were assessed with linear mixed-effects models and evaluated according to the Aβ-status so as to identify whether the effects were independent of Aβ status. Results:CCL2 rs4586-CC carriers exhibited a slower global Aβ-PET accumulation, particularly within stage I and stage II. However, they exhibited a faster accumulation of CSF P-tau and global tau-PET standard uptake value ratios, especially in Braak I and Braak III/IV and the inferior temporal gyrus. The congruent effects of CCL2 rs4586 on tau accumulation existed only in the Aβ–group, as is shown in global tau-PET and Braak I. However, CCL2 rs4586 was not associated with the cognitive decline. Conclusion:Our findings showed that the CCL2 rs4586-CC (versus TT/TC) genotype was associated with slower Aβ deposition and faster tau accumulation, and the latter of which was independent of Aβ status.
Keywords: Alzheimer’s disease, Alzheimer’s Disease Neuroimaging Initiative, amyloid-β, CCL2, tau
