Why some brain cells are more vulnerable in Alzheimer's
Official title: Mass spectrometry and multiplexed immunofluorescence imaging of metabolic and proteomic contributors to selective neuronal vulnerability in Alzheimer's disease
Funded at University of Rhode Island · NIH-11333165 · Data updated 2026-11-12
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 start | September 15, 2022 |
| Project end | May 31, 2027 |
| Funding year | 2025 |
| Award (this year) | $807,254 |
| NIH project number | 7R01AG078755-04 |
| Project ID | NIH-11333165 on NIH RePORTER |
Who could benefit from this research
✓Could help
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.
✕Less likely to help
Patients seeking immediate treatments or who cannot participate in brain donation are unlikely to receive direct benefit from this postmortem research.
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.
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 gone: 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
-
University of Rhode Island
Kingston, United States Active
Researchers
- Principal investigator: Varghese, Merina Thekenangarpadiyil — University of Rhode Island
- Study coordinator: Varghese, Merina Thekenangarpadiyil
Related research
Other NIH-funded projects on the same topics.
-
Understanding how brain activity changes may drive Alzheimer’s disease progression in a mouse model
Researchers are testing how changes in brain signals and protein cleanup processes affect the development of Alzheimer’s disease in mice.
-
Thiamine-boosting therapy for Alzheimer’s: understanding how benfotiamine may reduce harmful AGE in DP patients
A medication-based approach using high-dose vitamin B1 (benfotiamine) is studied to help people with Alzheimer's by reducing harmful sugar-related molecules.
-
Non-invasive tears biomarker for early Alzheimer's in LMICs
A low-cost, tear-based biomarker approach aims to detect early Alzheimer’s disease in older adults in Peru and similar settings.
-
Turning APOE4 into protective APOE2 or APOE3Christchurch to help with Alzheimer’s
A patient-facing explanation of a treatment idea that aims to change a genetic risk factor for Alzheimer's disease in the brain.
-
Telomerase in Alzheimer’s Disease: how aging biology could influence memory and brain health
Researchers are exploring a new brain-aging mechanism linked to telomerase, with potential to slow or modify Alzheimer’s disease in people and improve cognitive function.
-
Biomarkers of Alzheimer’s Disease: Sensory, Motor, and Cognitive Clues
Researchers are testing simple sensory and movement tasks to find early signs of Alzheimer’s disease so they can diagnose and treat people sooner.
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.