# Novel Protein Biomarkers of Corticolimbic Pathophysiology in Lewy body Dementia

> **NIH NIH U01** · EMORY UNIVERSITY · 2024 · $1,695,881

## Abstract

Project Summary
Lewy body dementia (LBD), a class of disorders comprising Parkinson’s disease dementia (PDD) and dementia
with Lewy bodies (DLB), features aggressive cognitive and neuropsychiatric decline without cure or effective
mitigating therapies. Driving the clinical challenges surrounding LBD is a poor understanding of the
pathophysiology underlying its clinical deterioration and a desperate lack of diagnostic, progressive, and
therapeutic biomarkers. Neuropathological evidence suggests that corticolimbic synucleinopathy is closely linked
to the aggressive dementia of LBD and that effective biomarkers of cognitive and neuropsychiatric decline would
necessarily reflect this corticolimbic dysfunction. Thus, our central hypothesis is that the corticolimbic LBD
brain features regional and disease-specific alterations in neuronal and non-neuronal pathways reflected
as unique protein signatures in CSF and plasma. To investigate this hypothesis, we will apply an integrated
network-based proteomic pipeline across brain, cerebrospinal fluid (CSF), and plasma to identify LBD biofluid
signatures anchored in corticolimbic pathophysiology. Our preliminary experience with this pipeline suggests it
is a powerful promoter of multiplexed biomarker assays reflective of diverse brain-based dysfunction, including
neuronal, glial, and endothelial pathophysiology. In addition to these proteomic experiments, we will also
establish an Emory LBD registry under the Parkinson’s Disease Biomarker Program (PDBP) and utilize its clinical
and biospecimen data to fuel proteomic validation studies and promote future LBD research. Our specific aims
include 1) building a longitudinal PDBP registry for LBD, 2) defining the corticolimbic network proteome of LBD,
3) performing brain-biofluid proteomic integration to identify promising biofluid markers, and 4) longitudinal
biofluid validation using targeted proteomic strategies. In addition to biospecimens collected in Aim 1, we will
supplement these experiments using existing brain and biofluid samples housed in Emory Goizueta Alzheimer’s
Disease Research Center biorepositories. Ultimately, our efforts to identify molecular signatures of cognitive and
neuropsychiatric decline in LBD promise to discover novel biomarkers to enhance early diagnosis, disease
monitoring, and gauging therapeutic response. Furthermore, such markers can serve as a necessary gateway
to effective drug therapies for this devastating spectrum of neurodegenerative diseases.

## Key facts

- **NIH application ID:** 10896269
- **Project number:** 5U01NS128433-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** ALLAN I LEVEY
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,695,881
- **Award type:** 5
- **Project period:** 2022-09-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896269

## Citation

> US National Institutes of Health, RePORTER application 10896269, Novel Protein Biomarkers of Corticolimbic Pathophysiology in Lewy body Dementia (5U01NS128433-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10896269. Licensed CC0.

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