Why some brain cells are more vulnerable in Alzheimer's
Mass spectrometry and multiplexed immunofluorescence imaging of metabolic and proteomic contributors to selective neuronal vulnerability in Alzheimer's disease
This work compares affected and relatively spared regions of donated brains to find chemical and protein changes that could help people with Alzheimer's.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Rhode Island NIH-funded |
| Lab location | 1 site (Kingston, United States) |
| Project ID | NIH-11333165 on NIH RePORTER |
What this research studies
We will analyze donated brain tissue from people with different stages of Alzheimer's and from controls, comparing the prefrontal cortex (often affected early) with the primary visual cortex (relatively spared). Using mass spectrometry imaging, the team will map small molecules and proteins across tissue sections and use segmentation to focus on pyramidal neurons. They will then apply multiplexed immunofluorescence on nearby sections to identify cell types and microenvironment changes and link those findings to clinical severity, pathology, and genetic risk. By registering data from both imaging methods, they aim to pinpoint metabolic pathways and protein signaling changes at regional, layer, and cellular levels.
Who could benefit from this research
Good fit: People diagnosed with Alzheimer's at various stages, and individuals without dementia who are willing to arrange brain donation after death, would be appropriate contributors to this work.
Not a fit: Patients seeking immediate treatments or who cannot participate in brain donation are unlikely to receive direct benefit from this postmortem research.
Why it matters
Potential benefit: If successful, this could reveal new markers or targets for earlier detection and therapies that protect vulnerable neurons in Alzheimer's.
How similar studies have performed: Related studies have used mass spectrometry and immunofluorescence on postmortem brain to highlight molecular changes in Alzheimer's, but combining both modalities across regions and layers at this scale is relatively novel.
Where this research is happening
Kingston, United States
- University of Rhode Island — Kingston, United States (Active)
Researchers
- Principal investigator: Varghese, Merina Thekenangarpadiyil — University of Rhode Island
- Study coordinator: Varghese, Merina Thekenangarpadiyil
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.