Soluble TREM2 and Alzheimer-related biomarker trajectories in the blood of patients with diabetes based on their cognitive status
Soluble TREM2 and Alzheimer-related biomarker trajectories in the blood of patients with diabetes based on their cognitive status
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DOI：
10.1016/j.diabres.2022.110121
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发表时间：
2022-11-02
影响因子：
5.1
通讯作者：
Tokuda, Takahiko
中科院分区：
文献类型：
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作者：
Satoh-Asahara, Noriko;Yamakage, Hajime;Tokuda, Takahiko
目的：我们的目的是阐明动态的血液生物标志物，根据2型糖尿病（DM）患者的认知功能障碍的严重程度，并确定有用的生物标志物糖尿病相关dementia.Methods：这是一个横断面，巢式病例对照研究121日本DM和非DM患者不同水平的认知功能。我们评估了参与者的认知功能，与阿尔茨海默病相关的血液生物标志物以及髓样细胞2（sTREM 2）上表达的可溶性触发受体。然后，我们比较了这些生物标志物之间的DM和非DM和跨不同的认知strature.Results：在所有的认知阶层，血清sTREM 2的水平显着较低的DM比非DM观察。我们还发现，在DM和非DM中，磷酸化tau（p-tau）的血浆水平随着认知下降水平的增加而增加。然而，这是伴随着血浆淀粉样蛋白-β（A β 42/A β 40的比例在非DM只有。结论：这项研究揭示了新的特征轨迹的痴呆相关的血液生物标志物在糖尿病相关的痴呆，这表明病理参与的分子级联启动受损的小胶质细胞活化。这导致血清sTREM 2降低，随后是没有实质性淀粉样蛋白斑块的tau蛋白病，其反映为血浆p-tau升高而A β 42/A β 40比率没有降低。
Aim: We aimed to elucidate the dynamics of blood biomarkers according to the severity of cognitive impairment in patients with type 2 diabetes mellitus (DM) and to identify useful biomarkers for diabetes-related dementia.Methods: This was a cross-sectional, nested case-control study of 121 Japanese DM and non-DM patients with different levels of cognitive functioning. We evaluated participants' cognitive functions, blood biomarkers related to Alzheimer's disease, and soluble triggering receptors expressed on myeloid cells 2 (sTREM2). We then compared these biomarkers between the DM and non-DM and across the different cognitive strata.Results: In all cognitive strata, significantly lower levels of serum sTREM2 were observed in the DM than in the non-DM. We also found that plasma levels of phosphorylated tau (p-tau) increased with increasing levels of cognitive decline in both the DM and non-DM. However, this was accompanied by a decrease in plasma amyloid-beta(A beta 42/A beta 40 ratios in non-DM only.Conclusion: This study revealed novel characteristic trajectories of dementia-related blood biomarkers in diabetes-related dementia, suggesting the pathological involvement of molecular cascades initiated by impaired microglial activation. This results in decreased serum sTREM2, followed by tauopathy without substantial amyloid plaques, reflected by plasma p-tau elevation with no decrease in the A beta 42/A beta 40 ratio.