Cerebral small vessel disease is one of the most common causes of cognitive decline and stroke. While several lines of evidence have established a relationship between inflammation and cerebrovascular pathology, the mechanistic link has not yet been elucidated. Recent studies suggest activation of immune mediators, including the soluble form of triggering receptor expressed on myeloid cells 2 (TREM2), may be critical regulators. In this study, we compared the plasma levels of soluble TREM2 and its correlations with neuroimaging markers and cerebral amyloid load in 10 patients with Alzheimer’s disease and 66 survivors of spontaneous intracerebral haemorrhage with cerebral amyloid angiopathy or hypertensive small vessel disease, two of the most common types of sporadic small vessel disease. We performed brain MRI and 11C-Pittsburgh compound B PET for all participants to evaluate radiological small vessel disease markers and cerebral amyloid burden, and 18F-T807 PET in a subgroup of patients to evaluate cortical tau pathology. Plasma soluble TREM2 levels were comparable between patients with Alzheimer’s disease and small vessel disease (P = 0.690). In patients with small vessel disease, plasma soluble TREM2 was significantly associated with white matter hyperintensity volume (P < 0.001), but not with cerebral amyloid load. Among patients with Alzheimer’s disease and cerebral amyloid angiopathy, plasma soluble TREM2 was independently associated with a tau-positive scan (P = 0.001) and white matter hyperintensity volume (P = 0.013), but not amyloid load (P = 0.221). Our results indicate plasma soluble TREM2 is associated with white matter hyperintensity independent of amyloid and tau pathology. These findings highlight the potential utility of plasma soluble TREM2 as a strong predictive marker for small vessel disease-related white matter injury and hold clinical implications for targeting the innate immune response when treating this disease.

中文翻译：

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血浆可溶性 TREM2 与独立于淀粉样蛋白和 tau 的白质病变相关

脑小血管疾病是认知能力下降和中风的最常见原因之一。虽然有几条证据已经建立了炎症和脑血管病理学之间的关系，但其机制联系尚未阐明。最近的研究表明，免疫介质的激活，包括在骨髓细胞 2 (TREM2) 上表达的可溶性触发受体，可能是关键的调节因子。在这项研究中，我们比较了 10 名阿尔茨海默病患者和 66 名患有脑淀粉样血管病或高血压小血管疾病的自发性脑出血幸存者（这是最常见的两种散发性小血管病的种类。我们对所有参与者进行了脑部 MRI 和 11C-匹兹堡化合物 B PET 以评估放射学小血管疾病标志物和脑淀粉样蛋白负荷，并在一个亚组患者中进行 18F-T807 PET 以评估皮质 tau 病理学。阿尔茨海默病和小血管疾病患者的血浆可溶性 TREM2 水平相当（P = 0.690）。在小血管疾病患者中，血浆可溶性 TREM2 与白质高信号量显着相关（P < 0.001），但与脑淀粉样蛋白负荷无关。在阿尔茨海默病和脑淀粉样血管病患者中，血浆可溶性 TREM2 与 tau 阳性扫描 (P = 0.001) 和白质高信号量 (P = 0.013) 独立相关，但与淀粉样蛋白负荷无关 (P = 0.221)。我们的结果表明，血浆可溶性 TREM2 与白质高信号相关，与淀粉样蛋白和 tau 病理学无关。这些发现突出了血浆可溶性 TREM2 作为小血管疾病相关白质损伤的强预测标志物的潜在效用，并在治疗该疾病时对靶向先天免疫反应具有临床意义。