Multi-Omics Analysis for Identifying Glial Dysfunction-Associated Genes as Therapeutic Targets and Drug Candidates in Alzheimer's Disease - PubMed

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder with unclear mechanisms and no disease-modifying therapies available.
Glial function is highlighted as crucial in AD pathogenesis, prompting a study to identify key AD-relevant cell populations and genes.
Single-cell transcriptomic data and GWAS summary statistics were integrated to identify AD-associated cell subtypes and genes.
Oligodendrocytes and astrocytes were identified as major cell types associated with AD genetic risk, with 27 candidate genes enriched in glial development and function.
QKI, ZBTB20, and C10orf90 were identified as key candidate genes through machine learning and validation across multiple datasets.
Single-cell analyses confirmed high expression of these genes in oligodendrocytes and astrocytes, with dynamic, stage-associated expression patterns.
Drug-gene interaction and molecular docking analyses identified retinoic acid as a potential therapeutic compound targeting QKI and ZBTB20.
The findings emphasize the role of oligodendrocytes and astrocytes in AD development and suggest new therapeutic strategies.

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