基础科学和病原发生学
Ajneesh Kumar1, Nicholas R Ray1, Jiji T Kurup1
1Columbia University Irving Medical Center, New York, NY, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
概括
阿尔茨海默病 (AD) 中的神经心理症状与抑郁症,精神分裂症和焦虑症有着共同的遗传联系. 像TMEM106B,ACE和ERC2这样的关键基因可能会驱动这些重叠的条件.
科学领域:
- 神经遗传学 神经遗传学
- 精神病学遗传学 精神病学遗传学
- 阿尔茨海默氏症疾病研究研究
背景情况:
- 神经精神症状 (NPS) 影响85%的阿尔茨海默氏病 (AD) 患者,恶化衰退和患者/护理人员的痛苦.
- 目前的NPS治疗缺乏有效性并产生不良影响,部分原因是对与初级精神疾病共享遗传学的理解不足.
研究的目的:
- 研究阿尔茨海默病 (AD) 和主要精神疾病 (抑郁症,精神分裂症,双相情感障碍,焦虑症) 之间的遗传重叠.
- 确定AD相关NPS的共同生物过程和基因驱动因素.
主要方法:
- 在AD和精神疾病的大规模GWAS总结统计数据上利用了局部遗传共变分析 (MiXeR,LAVA).
- 进行精细映射,in silico功能分析,并对已识别的重叠基因组位点进行序列数据分析.
主要成果:
- 确定了AD和抑郁症 (4),精神分裂症 (5),双相情感障碍 (3) 和焦虑症 (4) 之间共享的显著遗传位置.
- 精确的特定变体:一个TMEM106B误解变体 (与抑郁症/焦虑症共享),一个ACE调节变体 (与精神分裂症共享) 和ERC2变体 (与AD/焦虑症共享).
- 突出的基因功能:TMEM106B (溶酶体贩运),ACE (神经裂),ERC2 (神经递质释放).
结论:
- 在阿尔茨海默氏症和主要精神疾病之间确实存在类基因重叠.
- 确定了TMEM106B,ACE和ERC2作为AD相关NPS的关键共享遗传驱动因素.
- 强调需要进一步进行功能研究,以阐明潜在的生物机制.
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