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在阿尔茨海默氏病中,TREM2风险变异和相关的内分类型

Janna I R Dijkstra^1,2,3,4, Lisa Vermunt^5,6,7, Vikram Venkatraghavan^5,6

¹Genomics of Neurodegenerative Diseases and Aging, Department of Human Genetics, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands. j.i.r.dijkstra@amsterdamumc.nl.

Alzheimer's research & therapy

|March 6, 2025

概括

具有状细胞2 (TREM2) 基因变异表达触发受体的个体在阿尔茨海默病 (AD) 中表现出更快的认知衰退. 像R47H和T96K这样的特定变异与这种加速衰退和增加死亡风险有关.

科学领域:

神经科学是一个神经科学.
遗传学是一个遗传学.
生物化学生化学

背景情况:

肌肉细胞2 (TREM2) 基因表达的触发受体的罕见变异是阿尔茨海默病 (AD) 的重要危险因素.
针对TREM2蛋白的治疗策略正在开发中,用于AD.
TREM2变异对AD临床表型的确切影响在很大程度上仍未被描述.

研究的目的:

为了研究携带TREM2变体的阿尔茨海默病 (AD) 患者的临床和生物标志物特征.
为了比较TREM2变异携带者与非携带者在一个定义良好的AD队列中的表型.
探索与特定TREM2变异相关的临床测量中的潜在差异.

主要方法:

对123名TREM2变体携带者和1,459名非携带者,具有生物标志物确认的症状性AD的队列进行了临床和生物标志物数据的全面分析.
研究的特异TREM2变体包括R62H,R47H和T96K.
评估的措施包括认知评估 (MMSE,神经心理测试),MRI,CSF生物标志物,EEG和Tau-PET扫描.

主要成果:

在基线临床表现方面,TREM2变异携带者与非携带者没有区别.
在MMSE,大多数神经心理学领域,MRI,CSF生物标志物,EEG或Tau-PET扫描中没有发现显著差异.
TREM2 携带者表现出更快的全球认知衰退趋势 (p < 0.099).
R47H和T96K变异与更快的认知衰退 (p <0.05) 特别相关.
携带R47H的患者在诊断后死亡率增加 (p = 0.034).

结论:

虽然TREM2风险变体不会改变基线AD呈现,但它们与加速的全球认知衰退有关.
R47H和T96K变种似乎是这种加速下降的关键驱动因素.
了解变体特异性影响对于阐明TREM2在AD病变发生过程中的作用至关重要.
这种表型信息可以指导TREM2向疗法的临床开发.

关键词:

在TREM2中,我们可以使用TREM2.阿尔茨海默氏症是阿尔茨海默氏症的一种疾病.临床措施临床措施

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