# -Omics driven network analysis in Lewy Body dementia

> **NIH NIH U54** · MAYO CLINIC  JACKSONVILLE · 2020 · $624,533

## Abstract

PROJECT SUMMARY – PROJECT 1
Project 1 will focus on using –omics derived datasets to elucidate genetic factors and transcripts to predict the
pathways and networks underlying the etiology of Lewy body dementia (LBD). Aim 1 will build upon the
investigators previous studies. Our work has shown that the established common genetic susceptibility variants
do not drive either the α-syn or Aβ pathologic burden or the degree of neuronal cell loss observed in Lewy
body disorders. These data suggest that the genes and variants that drive disease progression and burden of
pathology may be different from those variants that increase the risk of disease. To examine this hypothesis,
we will analyze whole-genome sequence data for association with α-syn or Aβ pathologic burden and neuronal
cell loss in the nigra, and additional neuropathologic measures (as generated through the Pathology Core
[Core B]) for over 500 cases of our Lewy Body disease series. To complement these studies Aim 2 will perform
bulk RNA-Seq across all of the pathologic cases with varying levels of α-syn or Aβ burden, in an
unbiased approach, assess the levels of transcripts that are related to synuclein burden. In addition, a subset
of cases will be analyzed using single-nucleus RNAseq to examine the relationship between transcript level
and α-syn or Aβ pathologic burden categorized into distinct groups by Core B PI Dr. Dickson. These Aims will
help describe the genomic architecture driving LBD heterogeneity. The final Aim 3 will use these data to model
networks due to different LBD pathologies and to predict disease drivers. Aim 3 will also incorporate –omics
data generated within Project 2. Functional characterization of candidate genes, transcript and pathways
genes and the interaction with α-syn or Aβ and cellular readouts (e.g. autophagy, lysosomal dysfunction) will
be performed in collaboration with the PIs of Project 4.

## Key facts

- **NIH application ID:** 10022182
- **Project number:** 5U54NS110435-02
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** Owen A Ross
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $624,533
- **Award type:** 5
- **Project period:** 2019-09-20 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022182

## Citation

> US National Institutes of Health, RePORTER application 10022182, -Omics driven network analysis in Lewy Body dementia (5U54NS110435-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10022182. Licensed CC0.

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