New Research Grant Awarded: “Decoding Alzheimer’s Disease Mechanisms via Integrated Multi-Omics and O-GlcNAc Profiling.”
CADRC Clinical Core Leader, Dr. Brian Appleby, and collaborating researchers from NEOMED have been awareded $40k by the UH-NEOMED Brain Health Intramural Funding program for a new pilot research project titled “Decoding Alzheimer’s Disease Mechanisms via Integrated Multi-Omics and O-GlcNAc Profiling.”
The Team and The Project
The project is led by Principal Investigators Dr. Priya Raman, PhD (NEOMED) and Dr. Brian Appleby, MD (UH/CWRU). Their team, which includes co-investigators Dr. Erin Reed-Geaghan and Dr. Helen Piontkivska (NEOMED), is part of a collaborative effort across NEOMED, University Hospitals, Case Western Reserve University, and partner institutions.
Dr. Priya Raman
Dr. Brian Appleby
Dr. Erin Reed-Geaghan
Dr. Helen Piontkivska
What the Research Will Do
This research aims to uncover how metabolic dysfunction and vascular biology contribute to AD pathology and cognitive decline. The project will run from January 1, 2026, to December 31, 2026, and involves integrating multi-omic data:
- Integrated Multi-Omics: This combines proteomics and transcriptomics data.
- O-GlcNAc Profiling: This involves characterizing neuronal, glial, and vascular smooth muscle cell O-GlcNAc patterns.
The analysis will use human postmortem hippocampus and frontal lobe tissue sourced from the Cleveland Alzheimer’s Disease Research Center (CADRC) and the National Prion Disease Pathology Surveillance Center (NPDPSC).
The will link these molecular signatures to clinical AD features and neuropathologic staging, ultimately developing multi-omic datasets for future grant applications.
The Rationale: Why This Study Matters
Alzheimer’s disease frequently involves vascular pathology and metabolic dysfunction, yet the molecular mechanisms linking these processes to neurodegeneration remain unclear.
The core knowledge gap addressed is that O-GlcNAcylation in human AD brain vasculature has not been systematically studied, despite its key regulatory role in metabolism, inflammation, and protein modification.
The rationale is that understanding cell-type-specific O-GlcNAc dynamics and their relationship to multi-omic signatures may reveal:
- Early biomarkers
- Disease-driving pathways
- Therapeutic targets
- Precision medicine stratification frameworks
The project is also intended to generate preliminary data needed for future NIH and foundation funding proposals.
Where the Work Will Take Place
The research will occur at:
- Northeast Ohio Medical University (NEOMED)
- University Hospitals Cleveland Medical Center (UH/UHCMC)
It will utilize services from the Cleveland Clinic Proteomics Core and Novogene for sequencing and proteomics.
