Higher plasma soluble TREM2 correlates with reduced cerebral tau accumulation in Alzheimer’s disease

IF 9.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Guoyu Lan, Anqi Li, Fernando Gonzalez-Ortiz, Jieqin Lv, Wenqing Ran, Yue Cai, Pan Sun, Lin Liu, Jie Yang, Laihong Zhang, Zhengbo He, Lili Fang, Xin Zhou, Yalin Zhu, Zhen Liu, Xiang Fan, Xuhui Chen, Linsen Xu, Qingyong Wang, Xinlu Wang, Kun Sun, Guanxun Cheng, Ying Han, Kaj Blennow, Lu Wang, Pengcheng Ran, Tengfei Guo
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引用次数: 0

Abstract

Loss-of-function mutation of triggering receptor expressed on myeloid cell 2 (TREM2) is associated with increased risks for Alzheimer’s disease (AD). Recent animal studies reveal that the activation of peripheral TREM2 signaling may affect cerebral β-amyloid (Aβ) and tau aggregates. However, the underlying relationship between peripheral TREM2 and brain AD pathology has not yet been well-elucidated in the aging population. In this study, we collected 318 Chinese older adults with Aβ PET and plasma biomarker measures, including soluble TREM2 (sTREM2) and glial fibrillary acidic protein (GFAP), a proxy for astrocyte reactivity. Additionally, 129 participants underwent tau PET scans. We explored the association between plasma sTREM2, GFAP, and primary AD pathology. Plasma sTREM2 was negatively associated with reduced temporal tau PET burden in participants with abnormal Aβ and tau pathology. Higher plasma sTREM2 was related to the weaker association of Aβ pathology and plasma phosphorylated tau with tau PET increases. In contrast, elevated plasma GFAP was related to greater Aβ and tau PET burden along with stronger Aβ-related tau accumulation. Finally, higher plasma sTREM2 was linked to attenuated strength of the association between plasma GFAP and tau PET increases at both pre-defined regions of interest and voxel levels. Altogether, our findings suggest distinct relationships between plasma sTREM2 and GFAP with cerebral tau pathology, providing novel insights into the roles of peripheral TREM2 signaling and astrocytic reactivity in AD neuropathological development. This study has important implications, such as targeting the peripheral TREM2 signature, which may be a potential strategy for future AD therapies.

Abstract Image

高血浆可溶性TREM2与阿尔茨海默病大脑tau积聚减少相关
髓样细胞2 (TREM2)上表达的触发受体的功能缺失突变与阿尔茨海默病(AD)的风险增加有关。最近的动物研究表明,外周TREM2信号的激活可能影响大脑β-淀粉样蛋白(Aβ)和tau聚集物。然而,在老年人群中,外周TREM2与大脑AD病理之间的潜在关系尚未得到很好的阐明。在这项研究中,我们收集了318名中国老年人,进行了a β PET和血浆生物标志物测量,包括可溶性TREM2 (sTREM2)和胶质纤维酸性蛋白(GFAP),后者是星形胶质细胞反应性的代表。此外,129名参与者接受了tau PET扫描。我们探讨了血浆sTREM2、GFAP与原发性AD病理之间的关系。在Aβ和tau病理异常的参与者中,血浆sTREM2与颞部tau PET负担的减少呈负相关。血浆sTREM2升高与Aβ病理和血浆磷酸化tau蛋白与tau蛋白PET升高的相关性较弱有关。相比之下,血浆GFAP升高与Aβ和tau PET负担增加以及Aβ相关tau积聚增强有关。最后,在预定义的感兴趣区域和体素水平上,较高的等离子体sTREM2与等离子体GFAP和tau PET增加之间的关联强度减弱有关。总之,我们的研究结果表明血浆TREM2和GFAP与大脑tau病理之间存在明显的关系,为外周TREM2信号传导和星形细胞反应性在AD神经病理发展中的作用提供了新的见解。这项研究具有重要的意义,例如靶向外周TREM2信号,这可能是未来AD治疗的潜在策略。
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来源期刊
Molecular Psychiatry
Molecular Psychiatry 医学-精神病学
CiteScore
20.50
自引率
4.50%
发文量
459
审稿时长
4-8 weeks
期刊介绍: Molecular Psychiatry focuses on publishing research that aims to uncover the biological mechanisms behind psychiatric disorders and their treatment. The journal emphasizes studies that bridge pre-clinical and clinical research, covering cellular, molecular, integrative, clinical, imaging, and psychopharmacology levels.
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