Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Brain Behav. 2020 Apr;10(4):e01573. doi: 10.1002/brb3.1573. Epub 2020 Feb 19.
Triggering receptor expressed on myeloid cells-like transcript 2 gene (TREML2) is a newly identified AD susceptibility gene. Its missense variant rs3747742-C substantially decreases AD risk in both Caucasians and Han Chinese, but the underlying mechanisms remain elusive. In the present study, to uncover the possible mechanisms by which TREML2 rs3747742-C reduces AD risk, we investigated the possible relation of this variant with AD-related brain structures using a cognitively normal elderly population from Alzheimer's Disease Neuroimaging Initiative (ADNI) database.
In total, 158 cognitively normal elders from ADNI database with complete data for brain structures and TREML2 rs3747742 genotype were included in this study. The association of TREML2 rs3747742 genotype with the structures of three cerebral cortices (entorhinal cortex, middle temporal gyrus, and parahippocampal gyrus), two subcortical regions (amygdala and hippocampus), and three subfields of hippocampus (CA1, CA2 + CA3, and CA4 + dentate gyrus) was investigated.
A significant difference was noted in the volume of right CA1 subfield among three genotypes of TREML2 rs3747742 (p = .0364). In the multivariate analysis, TREML2 rs3747742-C significantly increased right CA1 subfield volume after adjusting for age, gender, education years, APOE ε4 status, and intracranial volume under the recessive genetic model (Bonferroni corrected p = .003586).
The present study provides the first evidence that TREML2 rs3747742-C carriers have larger volumes of hippocampal CA1 subfield in a cognitively normal elderly population. These findings imply that enhancement of brain reserve may contribute to the protection of TREML2 rs3747742-C in AD susceptibility.
髓样细胞触发受体样转录物 2 基因（TREML2）是一个新发现的 AD 易感基因。其错义变体 rs3747742-C 可显著降低白种人和汉族人群的 AD 风险，但潜在机制仍不清楚。在本研究中，为了揭示 TREML2 rs3747742-C 降低 AD 风险的可能机制，我们利用阿尔茨海默病神经影像学倡议（ADNI）数据库中的认知正常老年人队列，研究了该变体与 AD 相关脑结构的可能关系。
本研究共纳入 ADNI 数据库中 158 名认知正常的老年人，这些老年人具有完整的脑结构和 TREML2 rs3747742 基因型数据。研究了 TREML2 rs3747742 基因型与三个大脑皮质（内嗅皮质、颞中回和海马旁回）、两个皮质下区域（杏仁核和海马体）以及三个海马亚区（CA1、CA2+CA3 和 CA4+齿状回）的结构之间的关联。
TREML2 rs3747742 的三种基因型之间，右侧 CA1 亚区的体积存在显著差异（p=0.0364）。在多变量分析中，在调整年龄、性别、受教育年限、APOE ε4 状态和颅内体积后，TREML2 rs3747742-C 在隐性遗传模型下显著增加了右侧 CA1 亚区的体积（Bonferroni 校正后 p=0.003586）。
本研究首次提供了证据，表明在认知正常的老年人群中，TREML2 rs3747742-C 携带者的海马 CA1 亚区体积更大。这些发现表明，增强脑储备可能有助于保护 TREML2 rs3747742-C 免受 AD 的影响。
