Transcriptomic analysis of human brains with Alzheimer's disease reveals the altered expression of synaptic genes linked to cognitive deficits.
Transcriptomic analysis of human brains with Alzheimer's disease reveals the altered expression of synaptic genes linked to cognitive deficits.
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DOI：
10.1093/braincomms/fcab123
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发表时间：
2021
影响因子：
4.8
通讯作者：
Yan Z
中科院分区：
文献类型：
--
作者：
Williams JB;Cao Q;Yan Z
阿尔茨海默病是一种进行性神经退行性疾病，与记忆丧失和执行功能受损有关。导致阿尔茨海默病认知缺陷的分子基础尚不清楚。在这里，我们进行了交叉研究的大规模转录组分析的死后前额叶皮层来自阿尔茨海默氏症患者，以揭示异常基因表达在这种疾病中的作用。我们发现，阿尔茨海默病患者前额叶皮层最显著的变化之一是与突触功能相关的兴奋性和抑制性神经元中基因的下调，特别是SNARE结合复合物，这对囊泡对接和神经递质释放至关重要。将阿尔茨海默病的基因组数据与认知轨迹的蛋白质组数据进行比较，我们发现阿尔茨海默病中许多丢失的突触基因编码中枢蛋白，其增加的丰度是认知稳定性所必需的。这项研究揭示了与阿尔茨海默病相关的认知下降的治疗干预的潜在分子靶点。威廉姆斯及其同事对阿尔茨海默病患者进行了大规模的转录组学分析，并揭示了与突触功能相关的皮质神经元基因的下调，特别是SNARE结合复合物，作为阿尔茨海默病认知缺陷的关键分子决定因素。
Alzheimer’s disease is a progressive neurodegenerative disorder associated with memory loss and impaired executive function. The molecular underpinnings causing cognitive deficits in Alzheimer’s disease are loosely understood. Here, we performed cross-study large-scale transcriptomic analyses of postmortem prefrontal cortex derived from Alzheimer’s disease patients to reveal the role of aberrant gene expression in this disease. We identified that one of the most prominent changes in prefrontal cortex of Alzheimer’s disease humans was the downregulation of genes in excitatory and inhibitory neurons that are associated with synaptic functions, particularly the SNARE-binding complex, which is essential for vesicle docking and neurotransmitter release. Comparing genomic data of Alzheimer’s disease with proteomic data of cognitive trajectory, we found that many of the lost synaptic genes in Alzheimer’s disease encode hub proteins whose increased abundance is required for cognitive stability. This study has revealed potential molecular targets for therapeutic intervention of cognitive decline associated with Alzheimer’s disease. Williams and colleagues have performed large-scale transcriptomic analyses of Alzheimer’s disease patients and revealed the downregulation of genes in cortical neurons that are associated with synaptic functions, particularly the SNARE-binding complex, as the key molecular determinant for cognitive deficits in Alzheimer’s disease.
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DOI：
10.1083/jcb.137.7.1589
发表时间：
1997-06-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Prekeris R;Terrian DM
通讯作者：
Terrian DM
帕金森病患者黑质中 αB-晶状体蛋白表达的上调。
影响因子：
4.2
作者：
Liu, Yingjun;Zhou, Qinbo;Zhou, Jiawei
通讯作者：
Zhou, Jiawei
影响因子：
34.7
作者：
Burgoyne, Robert D.
通讯作者：
Burgoyne, Robert D.
影响因子：
25
作者：
Nativio R;Donahue G;Berson A;Lan Y;Amlie-Wolf A;Tuzer F;Toledo JB;Gosai SJ;Gregory BD;Torres C;Trojanowski JQ;Wang LS;Johnson FB;Bonini NM;Berger SL
通讯作者：
Berger SL
影响因子：
64.5
作者：
GEPPERT, M;GODA, Y;SUDHOF, TC
通讯作者：
SUDHOF, TC