# Identifying Pathophysiological Signatures of DLB Cognitive and Neuropsychiatric Decline Using a Systems-Based Proteomic Approach

> **NIH NIH K23** · EMORY UNIVERSITY · 2023 · $195,156

## Abstract

Project Summary / Abstract
Dr. Higginbotham is a promising physician-scientist who aspires to unravel the molecular pathophysiology
underlying the cognitive and neuropsychiatric decline of Dementia with Lewy bodies (DLB) and identify novel
protein signatures that help monitor and treat these debilitating symptoms. This K23 will advance her goals by
providing training and mentorship in the following core competencies: 1) bioinformatics; 2) molecular proteomic
techniques; and 3) clinical observational research. Dr. Higginbotham has assembled a mentoring team with
unparalleled expertise in these areas and their applications to neurodegeneration research. Her primary mentor,
Dr. Allan Levey, is a world-renowned cognitive neurologist who leads a highly productive laboratory with basic
and translational expertise in Alzheimer's disease (AD) research. Her co-mentor, Dr. Nicholas Seyfried, is an
expert in mass spectrometry (MS)-based proteomics and Director of the Emory Integrated Proteomics Core. She
will also work closely with a host of collaborators who will provide key biospecimen and analytical resources.
This project will use a systems-based proteomics approach to globally profile the corticolimbic
pathophysiology of DLB and identify protein signatures of this dysfunction in cerebrospinal fluid (CSF).
The rationale for these experiments stems from a staggering lack of biomarkers that assist in the monitoring and
treatment of DLB cognitive and neuropsychiatric decline. While synuclein accumulation in corticolimbic regions
correlates strongly to these devastating non-motor symptoms, little is known regarding the complex molecular
processes surrounding this pathology. Therefore, efforts to better define the corticolimbic pathophysiology
of DLB promise to not only enhance our scientific understanding of disease, but also promote the
discovery of novel molecular signatures that advance the clinical management of its cognitive and
neuropsychiatric decline. Dr. Higginbotham has spent the last two years optimizing brain-CSF integrative
proteomic strategies in AD. This work resulted in the identification of novel CSF AD protein signatures linked to
a diverse range of cortical pathophysiology. These exciting analyses comprise much of the pilot data for this
proposal and will serve as a template for its experiments in DLB. In Aim 1, Dr. Higginbotham will apply co-
expression network analysis to the DLB corticolimbic proteome to identify key disease-associated pathways.
She will then use co-immunoprecipitation MS to examine pathological synuclein interactors in disease. In Aim 3,
she will measure protein signatures of this brain-based pathophysiology in DLB CSF. Based on preliminary data,
Dr. Higginbotham hypothesizes that the cortical and limbic regions of the DLB brain feature altered protein
pathways and synuclein interactors involved in cellular metabolism. She also expects this corticolimbic
pathophysiology to manifest in the CSF as unique DLB protein sig...

## Key facts

- **NIH application ID:** 10579233
- **Project number:** 5K23NS119964-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Lenora Higginbotham
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $195,156
- **Award type:** 5
- **Project period:** 2022-03-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10579233

## Citation

> US National Institutes of Health, RePORTER application 10579233, Identifying Pathophysiological Signatures of DLB Cognitive and Neuropsychiatric Decline Using a Systems-Based Proteomic Approach (5K23NS119964-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10579233. Licensed CC0.

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