Integrated genomic meta-analysis identifies cell-type-specific signatures and targets in early Alzheimer's disease

This study conducted an integrated genomic meta-analysis to better understand cellular mechanisms in early Alzheimer's disease. Researchers systematically reviewed and integrated multiomic data using the computational method MAIC. They found that electron transport chain dysfunction in mitochondria is a shared pathway in neurons, microglia, and astrocytes. Wnt signalling was identified as a prominent astrocyte-specific signature. Pathological neuro-glial signalling mechanisms included APP-CD74, APOE-SORL1, and WNT-FZD/LRP6. Integration with pharmacological data revealed therapeutics already under investigation for Alzheimer's disease, such as guanfacine. Additionally, candidates not previously prioritized, such as eltrombopag and encorafenib, were identified. The analysis aims to prioritize pathways for investigation and therapeutics for repurposing in early Alzheimer's disease.