How H1 versus H2 MAPT genetic backgrounds change brain cells in frontotemporal dementia and PSP
Project 2: Impact of H1/H2 haplotypes on cellular disease-associated phenotypes driven by FTD-causing MAPT mutations
This work looks at how two common genetic backgrounds near the MAPT gene (H1 and H2) change disease-related behavior of brain cells in people with frontotemporal dementia or progressive supranuclear palsy.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Icahn School of Medicine at Mount Sinai NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project ID | NIH-11170012 on NIH RePORTER |
What this research studies
From my perspective as a patient, researchers are comparing the H1 and H2 haplotypes at the 17q21.31/MAPT region to see how they alter gene activity tied to frontotemporal dementia (FTD-tau) and progressive supranuclear palsy (PSP). They will use lab-grown human brain cells and molecular tools such as ATAC-seq, 3-D genome mapping, and massively parallel reporter assays (MPRA) to read chromatin accessibility and regulatory activity driven by common and rare variants. The team will study how MAPT disease-causing mutations behave differently depending on the haplotype background and aim to pinpoint specific causal variants that change cell function. Findings may come from patient-derived samples or cellular models created from patient genetic material.
Who could benefit from this research
Good fit: Ideal candidates include people diagnosed with FTD-tau or PSP, known carriers of MAPT mutations, or relatives willing to provide genetic samples and clinical information.
Not a fit: People whose dementia is not related to MAPT mutations, or those unwilling to provide genetic material or samples, are unlikely to gain direct benefit from this project.
Why it matters
Potential benefit: If successful, this work could explain why some MAPT mutations cause different disease forms and point to targets for better diagnostics or treatments.
How similar studies have performed: Previous GWAS and functional genomic studies have implicated the 17q21.31/MAPT region and used MPRA and epigenomic assays to find regulatory variants, but applying these methods to haplotype-specific effects on MAPT mutations is relatively new.
Where this research is happening
New York, United States
- Icahn School of Medicine at Mount Sinai — New York, United States (Active)
Researchers
- Principal investigator: Geschwind, Daniel H — Icahn School of Medicine at Mount Sinai
- Study coordinator: Geschwind, Daniel H
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.