How TDP-43 protein clumps and double-stranded RNA are linked in Alzheimer's and frontotemporal dementia
Defining the pathogenic relationship of TDP-43 inclusions and cytoplasmic double stranded RNA in AD and FTD
This project looks at whether clumps of the protein TDP-43 and abnormal double-stranded RNA appear together in brains of people with Alzheimer's disease or frontotemporal dementia and how that might relate to faster memory loss.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Harvard Medical School NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project ID | NIH-11297531 on NIH RePORTER |
What this research studies
From a patient's point of view, researchers will study brain tissue donated after death from people who had Alzheimer's disease or frontotemporal dementia. They will use a high-content imaging method called tissue-based cyclic immunofluorescence (t-CyCIF) to map where TDP-43 protein inclusions and cytoplasmic double-stranded RNA (cdsRNA) occur in the same cells. The team will compare many autopsy brains, including cases with the C9ORF72 genetic change, to see whether cdsRNA and TDP-43 inclusions coincide and whether that relates to immune signaling linked to decline. Findings will be compared to earlier laboratory work suggesting cdsRNA activates type I interferon responses.
Who could benefit from this research
Good fit: People with a diagnosis of Alzheimer's disease or frontotemporal dementia who are willing to join a brain donation or tissue-provision program would be appropriate contributors to this work.
Not a fit: People without Alzheimer's or FTD, or those not enrolled in brain donation programs, are unlikely to directly participate or receive immediate benefit from this grant.
Why it matters
Potential benefit: If successful, this work could reveal a biological link that explains why TDP-43 makes dementia progress faster and point to new biomarkers or targets for therapies.
How similar studies have performed: Prior studies have shown TDP-43 is associated with worse cognition and that dsRNA can trigger immune responses in models, but applying multiplexed imaging to map their overlap in many human AD and FTD brains is a newer approach.
Where this research is happening
Boston, United States
- Harvard Medical School — Boston, United States (Active)
Researchers
- Principal investigator: Albers, Mark W — Harvard Medical School
- Study coordinator: Albers, Mark W
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.