How APOE type and Alzheimer's changes affect individual brain cells
Project 4: Cross-species Dissection of Cellular Response to APOE Genotype and AD Pathology Using Single-cell Multi-omics
This project looks at how the APOE ε4 gene and Alzheimer’s-related proteins change single brain cells across species to guide better tests and treatments for people with or at risk for Alzheimer’s.
Quick facts
| Grant type | P01 program project |
|---|---|
| Study type | NIH-funded research |
| Funding institution | J. David Gladstone Institutes NIH-funded |
| Lab location | 1 site (San Francisco, United States) |
| Project ID | NIH-11166579 on NIH RePORTER |
What this research studies
Researchers will use single-cell multi-omics (including single-cell RNA and ATAC sequencing) to profile individual neurons and glia from animal models and human samples. They will compare effects of APOE genotypes, amyloid-beta, and tau pathology across brain regions to map cell-type specific responses. The team will link these cellular changes to prolonged neural network dysfunction and related signs like subclinical epileptiform activity. Findings will be integrated across species to highlight conserved pathways that could become targets for therapies or biomarkers.
Who could benefit from this research
Good fit: People with Alzheimer’s disease, individuals at risk because they carry the APOE ε4 variant, or people willing to donate brain tissue or other samples to research may be appropriate to contribute to this work.
Not a fit: People without Alzheimer’s pathology or APOE-related risk, and anyone seeking an immediate treatment, are unlikely to gain direct clinical benefit from this basic mechanistic research in the short term.
Why it matters
Potential benefit: If successful, this work could reveal specific cell types and molecular pathways to target for new therapies or early biomarkers for people with APOE ε4 or Alzheimer’s disease.
How similar studies have performed: Prior single-cell studies have identified cell-type changes in Alzheimer’s, but a large cross-species, APOE-focused single-cell multi-omics integration at this scale is relatively novel.
Where this research is happening
San Francisco, United States
- J. David Gladstone Institutes — San Francisco, United States (Active)
Researchers
- Principal investigator: Corces, Michael Ryan — J. David Gladstone Institutes
- Study coordinator: Corces, Michael Ryan
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.