# Reelin' from Alzheimer's Disease

- **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:** [Tamara Vasilkovska](https://cerebralvalley.ai/u/tvasilkovska)
- **GitHub:** https://github.com/TamaraVas/reln_rorb_AD_analysis
- **Demo video:** https://www.youtube.com/watch?v=gGaSG9FV90c
- **Gallery:** https://cerebralvalley.ai/e/built-with-claude-life-sciences/hackathon/gallery
- **Page:** https://cerebralvalley.ai/e/built-with-claude-life-sciences/hackathon/gallery/175

Which neurons die first in Alzheimer's, and why those? I investigated whether two markers of the selectively vulnerable entorhinal-cortex neurons that seed tau pathology — Reelin (RELN) and the transcription factor RORB — occupy the same individual cells, and whether that co-occupancy tracks disease. Using Claude Science, I built the analysis end to end: harmonizing ten public human datasets across single-cell, spatial (MERFISH), and bulk transcriptomics (>4M cells) and fitting depth-controlled, donor-clustered models that test the two genes as a pair.
The findings show that RELN⁺/RORB⁺ detection is independent in healthy tissue but converges with advancing tau stage — a monotonic six-stage dose-response, independently replicated in an 81-donor cohort with 10× higher depth (exactly the condition that would inflate a detection artifact — which it doesn't), confirmed in intact tissue by MERFISH, absent in other tauopathies, and amplified by APOE-ε4 dose. Regulatory-network, ChIP-seq, and structural analyses rule out a direct molecular link, establishing co-vulnerability rather than partnership.
This sharpens the map of AD's earliest-lost neurons and ties it to APOE4 — the field's strongest genetic risk factor — via Reelin–ApoE receptor competition: a hypothesis-generating finding, with the decisive next experiments specified, that others can build on directly.

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