# Contribution of the interaction between synuclein and tau in the pathophysiology of dementia with Lewy bodies

> **NIH NIH F30** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $46,069

## Abstract

Project Summary
This application is for F30 support of Lindsay Stoyka during the laboratory phase of her MD/PhD
training.
 The scientific focus of the proposal is to examine how endogenous microtubule binding protein tau
interacts with pathologic variants of alpha-synuclen to lead to cellular dysfunction and death, alpha-synuclein
aggregation, and cognitive decline in Dementia with Lewy Bodies (DLB). DLB is the second most common
cognitive disorder in the elderly and is characterized by fluctuating cognitive performance, visuospatial
impairment, and frontosubcortical dysfunction. Intracellular aggregates of alpha-synuclein (termed Lewy
bodies) are found in neurons throughout the deep cortical layers, paralimbic, and neocortical structures of DLB
patients. The rationale behind the present proposal is that tau has been shown to bind to alpha-synuclein
fibrils, but not monomer, suggesting a pathogenic interaction that is nonexistent in the non-diseased state.
Additionally, Lewy body presence in the basal forebrain and limbic areas correlate with deteriorating cognitive
function in humans. A clear synergistic effect of pathogenic alpha-synuclein and tau have been shown both in
vitro and in vivo. However, few studies have explored the role of endogenous tau on alpha-synuclein
aggregation in a DLB model. Determining the mechanisms at play in Lewy Body formation will facilitate the
development of appropriate and specific therapies for DLB patients.
 The proposed training plan for Lindsay Stoyka is sponsored by her project mentors, Dr. David
Standaert and Dr. Volpicelli-Daley. The overall goal of the training plan is to provide the PI with a solid
foundation for a successful career as a physician scientist. A project based both in translational approaches,
while focused on a disease-oriented pathogenesis, is the ideal training environment for any aspiring physician
scientist.
 Included in the training plan are experiences that help the PI: 1) gain competence in a variety of
techniques in neurobiology 2) collaborate with other scientists, 3) develop hypothesis-driven research, 4)
present data in a written and oral format, 5) effectively integrate research with clinic, and 6) responsibly
conduct research.

## Key facts

- **NIH application ID:** 9969302
- **Project number:** 5F30AG058458-03
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Lindsay Elizabeth Stoyka
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $46,069
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969302

## Citation

> US National Institutes of Health, RePORTER application 9969302, Contribution of the interaction between synuclein and tau in the pathophysiology of dementia with Lewy bodies (5F30AG058458-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9969302. Licensed CC0.

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