Tan Yi Jayne, Ng Adeline S L, Vipin Ashwati, Lim Joseph K W, Chander Russell J, Ji Fang, Qiu Yingwei, Ting Simon K S, Hameed Shahul, Lee Tih-Shih, Zeng Li, Kandiah Nagaendran, Zhou Juan
Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Programme, Duke-NUS Medical School, Singapore.
Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore.
J Alzheimers Dis. 2017;58(2):413-423. doi: 10.3233/JAD-161277.
Variants in triggering receptor expressed on myeloid cells 2 (TREM2) are associated with increased Alzheimer's disease (AD) risk. Recent studies have reported inconsistent peripheral TREM2 mRNA expression levels and relationship with cognitive scores in AD and mild cognitive impairment (MCI). Additionally, no study has examined the association of peripheral TREM2 levels with neuroimaging measures in AD and MCI.
To determine peripheral TREM2 mRNA levels in AD, amnestic MCI (aMCI) and healthy controls, and the association with cognitive performance and brain structural changes.
We measured peripheral TREM2 mRNA levels in 80 AD, 30 aMCI, and 86 healthy controls using real time polymerase chain reaction. TREM2 levels were correlated with various cognitive performance and brain volumes, correcting for APOE4 status.
TREM2 mRNA levels were significantly higher in AD compared to controls and aMCI. Levels did not differ between aMCI and controls. Corrected for APOE4, higher TREM2 levels correlated with lower Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA) and episodic memory scores, and lower total grey matter and right hippocampal volumes. Whole-brain voxel-based morphometry analysis found negative association between TREM2 mRNA levels and grey matter volumes in temporal, parietal and frontal regions. AD subjects with MoCA scores ≤20 had higher TREM2 levels correlating with smaller total grey matter, left hippocampal and right hippocampal volumes.
Peripheral TREM2 mRNA levels are higher in AD and are associated with AD-related cognitive deficits and hippocampal atrophy. Our findings suggest that TREM2 may be a potential non-invasive peripheral biomarker for AD diagnosis.
髓系细胞触发受体2（TREM2）的变异与阿尔茨海默病（AD）风险增加相关。最近的研究报告了AD和轻度认知障碍（MCI）患者外周血TREM2 mRNA表达水平不一致，以及与认知评分的关系。此外，尚无研究探讨AD和MCI患者外周血TREM2水平与神经影像学指标的相关性。
确定AD、遗忘型MCI（aMCI）和健康对照者外周血TREM2 mRNA水平，以及与认知表现和脑结构变化的相关性。
我们使用实时聚合酶链反应测量了80例AD患者、30例aMCI患者和86名健康对照者外周血TREM2 mRNA水平。TREM2水平与各种认知表现和脑容量相关，并校正了APOE4状态。
与对照组和aMCI相比，AD患者的TREM2 mRNA水平显著更高。aMCI和对照组之间的水平没有差异。校正APOE4后，较高的TREM2水平与较低的简易精神状态检查表、蒙特利尔认知评估（MoCA）和情景记忆评分相关，以及较低的全脑灰质和右侧海马体积。基于体素的全脑形态学分析发现，TREM2 mRNA水平与颞叶、顶叶和额叶的灰质体积呈负相关。MoCA评分≤20的AD患者TREM2水平较高，与较小的全脑灰质、左侧海马和右侧海马体积相关。
AD患者外周血TREM2 mRNA水平较高，且与AD相关的认知缺陷和海马萎缩有关。我们的研究结果表明，TREM2可能是一种潜在的用于AD诊断的非侵入性外周生物标志物。
