Transcriptomic analysis of human brains with Alzheimer’s disease reveals the altered expression of synaptic genes linked to cognitive deficits

Abstract 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 analys...

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Published in:Brain communications 2021-01, Vol.3 (3), p.fcab123-fcab123
Main Authors: Williams, Jamal B, Cao, Qing, Yan, Zhen
Format: Article
Language:English
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Summary:Abstract 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. Graphical Abstract Graphical Abstract Video Abstract 10.1093/braincomms/fcab123_video1 Video Abstract fcab123media1 6264876412001
ISSN:2632-1297
2632-1297
DOI:10.1093/braincomms/fcab123