Department of Neurology, Peking University First Hospital, Peking University, Beijing, China.
Department of Neurology, Pujiang Branch, The First Affiliated Hospital of Zhejiang University, Zhejiang, China.
J Alzheimers Dis. 2022;88(1):117-126. doi: 10.3233/JAD-220102.
Recently it has been proposed that microglial response has a stage-dependent effect on the progression of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) sTREM2 has emerged as a promising microglial activation marker.
To test the stage-dependent role of microglia by studying the association between baseline sTREM2 and dynamic brain structural changes in AD and mild cognitive impairment (MCI) patients.
22 amyloid-β-positive (A+) and tau-positive (T+) AD and 24 A+T+MCI patients were identified from the Alzheimer's Disease Neuroimaging Initiative. The patients had baseline CSF amyloid-β, phosphorylated-tau, and sTREM2, and were followed up for at least one year by T1-weighted and diffusion tensor imaging scans. Gray matter volumes and white matter microstructural integrity were evaluated. Linear mixed models were applied to analyze how baseline sTREM2 may influence the rate of brain structural changes while adjusting for the effects of age, APOE4 status, and the CSF core markers.
In A+T+AD patients, baseline CSF sTREM2 was associated with faster mean diffusivity increase in the bilateral posterior corona radiata and right superior longitudinal fasciculus. In A+T+MCI patients, baseline CSF sTREM2 was associated slower gray matter volumetric loss in parahippocampal gyrus, left fusiform cortex, left middle temporal gyrus, and left lateral occipital cortex. Baseline CSF sTREM2 also had a protective effect against mean diffusivity increase in right inferior fronto-occipital fasciculus, left superior longitudinal fasciculus, left forceps minor, and left uncinate fasciculus.
Microglial activation at early stage might have a protective effect against neurodegeneration, while at late stage it might facilitate AD. Future efforts on modulating microglial activation could be promising, given a carefully selected time window for intervention.
最近有人提出，小胶质细胞反应对阿尔茨海默病（AD）的进展有阶段性影响。脑脊液（CSF）sTREM2 已成为一种有前途的小胶质细胞激活标志物。
通过研究 AD 和轻度认知障碍（MCI）患者基线 sTREM2 与大脑结构动态变化之间的关系，测试小胶质细胞的阶段性作用。
从阿尔茨海默病神经影像学倡议中确定了 22 名淀粉样蛋白-β 阳性（A+）和 tau 阳性（T+）AD 患者和 24 名 A+T+MCI 患者。这些患者有基线 CSF 淀粉样蛋白-β、磷酸化 tau 和 sTREM2，并通过 T1 加权和弥散张量成像扫描至少随访一年。评估灰质体积和白质微观结构完整性。应用线性混合模型分析基线 sTREM2 如何在调整年龄、APOE4 状态和 CSF 核心标志物的影响后，影响大脑结构变化的速度。
在 A+T+AD 患者中，基线 CSF sTREM2 与双侧后冠状辐射和右侧上纵束的平均弥散率增加呈正相关。在 A+T+MCI 患者中，基线 CSF sTREM2 与海马旁回、左侧梭状回、左侧颞中回和左侧外侧枕叶灰质体积减少呈负相关。基线 CSF sTREM2 对右侧下额枕下束、左侧上纵束、左侧小钳和左侧钩束的平均弥散率增加也有保护作用。
早期小胶质细胞激活可能对神经退行性变具有保护作用，而晚期则可能促进 AD。鉴于干预的时间窗口选择得当，未来对调节小胶质细胞激活的努力可能具有广阔的前景。
