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Exploring Drug-Gene Interactions in Alzheimer's: Insights from Epidemiology and Lipid Metabolism

This meeting review highlights research on the correlation between epidemiology and JAK/STAT pathways in Alzheimer's disease, as well as lipid metabolism influenced by Aβ and τ contrasts. The work presented by Alejo J. Nevado-Holgado from Simon Lovestone’s lab covers systematic drug analyses, anti-inflammatories, cognitive function, and future research strategies.

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Exploring Drug-Gene Interactions in Alzheimer's: Insights from Epidemiology and Lipid Metabolism

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  1. F2F meeting Sept 2016 Work from: Simon Lovestone’s lab Presenting: Alejo J Nevado-Holgado 1) Epidemiology correlated with JAK/STAT 2) Aβ/τ contrast enriches lipids and comp. 3) Lipid metabolism in Aβ/τ contrast (Alison Braid) 4) Systematic analysis of drugs in real world data (Chi-Hun Kim) 15/10/14

  2. Epidemiology correlated with JAK/STAT

  3. Aβ/τcontrast enriches lipids and comp.

  4. Anti-inflammatories & better cognition

  5. Work status in WP1 • Publications funded by the consortium: • JAK-STAT correlates how protective inflammatory diseases are to Alzheimer’s disease. In preparation. • Pathways at the intersection of AD and NSAIDs. CSBJ. • Commonly prescribed drugs associate with cognitive function: a cross-sectional study in UK Biobank. BMJ Open. • Enrichment of Aβ/τ contrast. In preparation. • Plan for next year, following SAB feedback • Study whether C-Map and epidemiology further support CSF1R, P2X7 & TYK2 • In future wet-lab validation, use co-cultures and positive controls

  6. C-Map and epidemiology: Strategy • US Ambulatory records: • 250K patients, 8 drugs max • Cmap: • ~1500 drugs, 3 lines

  7. C-Map and epidemiology: Strategy Gene – Drug associations Drug – AD associations Gene – AD

  8. Selecting relevant drugs in C-Map

  9. Selecting relevant diseases in EHRs

  10. Genes that are affected by drugs apparently protective for AD

  11. Work status in WP1 • Next steps • Compile a list of drugs affecting CSF1R and TYK2 to different degrees and directions • Increase the number of patients on the US Ambulatory Records, from 250K to 1M or more • Investigate whether TYK2-AD and CSF1R-AD effects are strongest in some types of patients, but weaker in others. • If results are positive, attempt wet-lab validation.

  12. Many thanks!

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