# GBA pathway markers for Lewy body dementias

> **NIH NIH U01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $571,262

## Abstract

Dysfunction of the β-glucocerebrosidase gene (GBA) pathway is genetically, neuropathologically, and
biochemically implicated in Lewy body dementias. GBA pathway-directed markers and treatments offer an
opportunity for rapidly implementing proof-of-concept trials of drugs designed to slow disease progression. A
tool kit of tests is needed for biomarkers-guided go/no-go decisions that includes molecular biomarkers for target
engagement, drug response, and disease progression.
 In Aim 1, we will determine, whether disruption of the GBA pathway in plasma and cerebrospinal fluid is
specifically associated with Lewy body dementias in a large, cross-sectional study of 435 individuals with Lewy
body dementias, healthy controls, and disease controls with other dementias using targeted, quantitative mass
spectrometry assays for fifty pathway sphingolipids and an assay for β-glucocerebrosidase activity. Moreover,
we will explore whether quantitative or qualitative changes in the GBA pathway inform on GBA mutation status,
clinical disease severity, and clinical diagnosis. In Aim 2, we will determine, whether GBA pathway markers
longitudinally track disease progression in Lewy body dementias. In Aim 3, we will longitudinally collect clinical
data, CSF, and blood samples of 100 patients with DLB, PDD and controls from Harvard-affiliated hospitals and
expand the NINDS Parkinson's Disease Biomarkers Program collection.
 These analyses will translate genetic clues into clinical trials markers. They will create the tools needed
for innovative, genetics-inspired, biomarkers-guided phase II trials for Lewy body dementias and generally
enrich the PDBP resource.

## Key facts

- **NIH application ID:** 10023952
- **Project number:** 5U01NS100603-05
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** CLEMENS R SCHERZER
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $571,262
- **Award type:** 5
- **Project period:** 2016-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10023952

## Citation

> US National Institutes of Health, RePORTER application 10023952, GBA pathway markers for Lewy body dementias (5U01NS100603-05). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/10023952. Licensed CC0.

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