Gao Fan, Zhang Peng-Fei, Gao Jing, Song Jinghui, Chi Song
Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Medicine, Hangzhou Juno Genomics Inc, Hangzhou, China.
J Alzheimers Dis. 2022;90(4):1647-1657. doi: 10.3233/JAD-220716.
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.
We aimed to investigate whether CCL2 rs4586 SNP is associated with the pathological changes and cognitive decline of AD.
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.
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.
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.
CC趋化因子配体2（CCL2）是小胶质细胞激活的关键免疫调节趋化因子，与阿尔茨海默病（AD）的发病机制有关。CCL2单核苷酸多态性（SNP）与AD风险之间的关联仍存在争议。
我们旨在研究CCL2 rs4586 SNP是否与AD的病理变化和认知衰退相关。
本研究纳入了486名来自阿尔茨海默病神经影像学倡议组织的参与者，他们有纵向脑脊液（CSF）淀粉样蛋白-β（Aβ）和磷酸化tau蛋白（P-tau）生物标志物、18F-氟比他班和18F-氟代tau蛋白正电子发射断层扫描（PET）以及认知评估数据。采用线性混合效应模型评估CCL2 rs4586 SNP对AD病理变化和认知衰退的影响，并根据Aβ状态进行评估，以确定这些影响是否独立于Aβ状态。
CCL2 rs4586-CC携带者的整体Aβ-PET积累较慢，尤其是在I期和II期。然而，他们的CSF P-tau和整体tau-PET标准摄取值比率积累较快，特别是在Braak I和Braak III/IV以及颞下回。CCL2 rs4586对tau积累的一致性影响仅存在于Aβ组，如在整体tau-PET和Braak I中所示。然而，CCL2 rs4586与认知衰退无关。
我们的研究结果表明，CCL2 rs4586-CC（相对于TT/TC）基因型与较慢的Aβ沉积和较快的tau积累相关，且后者独立于Aβ状态。
