# Mickey Pentecost

- **Event:** [Built with Claude: Life Sciences](https://cerebralvalley.ai/e/built-with-claude-life-sciences)
- **When:** Jul 7 at 12:00 PM – Jul 14 at 12:00 AM (EDT)
- **Where:** Online
- **Team:** [Mickey Pentecost](https://cerebralvalley.ai/u/MickeyP)
- **GitHub:** https://github.com/mickeypentecost/microglial-tbi-ad-axis/blob/main/SUBMISSION.md
- **Demo video:** https://youtu.be/LplLZ6PIfbU
- **Gallery:** https://cerebralvalley.ai/e/built-with-claude-life-sciences/hackathon/gallery
- **Page:** https://cerebralvalley.ai/e/built-with-claude-life-sciences/hackathon/gallery/10

Traumatic brain injury and inherited genetic risk both raise the odds of Alzheimer's, but no one had shown they act through the same mechanism. 

Working only from public data, I pre-specified two opposing gene programs in microglia ( an inflammatory "accelerator" and a pro-resolving "brake") and tested whether injury and inherited risk converge on the same one.

They do. 

Across nine analyses spanning human AD, mouse TBI, chronic traumatic encephalopathy, single-nucleus and bulk RNA, spatial transcriptomics, and brain proteomics, the accelerator program is elevated in both conditions and concentrates spatially at the injury lesion and around amyloid plaques. Partitioned heritability shows 31% of inherited AD risk falls on microglial regulatory DNA (1.5% of the genome, 21-fold enrichment) and loads specifically onto the accelerator arm while avoiding the brake, a directional genetic test made possible by pre-specifying both modules. Critically, inherited risk enters upstream (APOE, TREM2), while the downstream effector genes are installed by injury or disease itself: TBI installs environmentally what AD risk alleles predispose to genetically. Both arms are read out at a single receptor, CD44, whose elevation reproduces across four independent modalities and both species.

Why it matters: the work turns an unexplained epidemiological link into a defined molecular circuit with ranked, testable therapeutic predictions, and it does so entirely from existing public datasets reanalyzed through one harmonized pipeline, making it a reusable resource rather than a one-off result.

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Markdown version of https://cerebralvalley.ai/e/built-with-claude-life-sciences/hackathon/gallery/10. Site index for agents: https://cerebralvalley.ai/llms.txt · full text: https://cerebralvalley.ai/llms-full.txt