# Drosophila models to study Prion-like propagation of the protein aggregates that characterize Alzheimer's and Parkinson's disease

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2020 · $427,625

## Abstract

The common neurodegenerative disorders Alzheimer’s disease (AD) and Parkinson’s disease
(PD) are both characterized by the accumulation and spread of protein aggregates through the
nervous system. As in prion disorders, the protein aggregates that occur in AD and PD are
believed to propagate by transfer of aggregate seeds to recipient cells, where the seeds serve as
templates for conversion of their normally folded counterparts into aggregating forms. The spread
of protein aggregates is accepted as an essential part of the pathogenesis of both AD and PD,
yet none of the more than 100 loci that influence the risk of AD and PD are known to affect the
spread of protein aggregates between tissues, and the underlying mechanisms are poorly
understood. One reason for this gap in understanding is the scarcity of genetically tractable in
vivo model systems for studying propagation and spread of aggregated tau and alpha-synuclein,
two key aggregate-prone proteins in AD and PD. The goal of this pilot project grant is to develop
a simple, modular, and highly tractable set of Drosophila models to study the spread of protein
aggregation. First, we will create transgenic lines that will permit us to express multiple
combinations of WT and mutant forms of tau and alpha-synuclein. We will then use these lines to
express the WT forms of these proteins at low levels throughout the nervous system, while
overexpressing WT or mutant forms of the same protein in a small subset of cells to initiate
aggregation. Using epitope tags to distinguish the products of the transgenes, we will visualize
and quantify the resulting spread of aggregates. This set of transgenic lines will facilitate rapid
investigation of the effects of previously identified genetic risk factors and candidate cellular
pathways on the spread of protein aggregates in neurodegenerative disease. Our system will thus
advance understanding of the mechanisms underlying the spread of protein aggregates in AD
and PD, which in turn may reveal new targets for therapeutic intervention in these common and
debilitating disorders.

## Key facts

- **NIH application ID:** 10107351
- **Project number:** 1R21AG070374-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Leo J Pallanck
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $427,625
- **Award type:** 1
- **Project period:** 2020-09-11 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10107351

## Citation

> US National Institutes of Health, RePORTER application 10107351, Drosophila models to study Prion-like propagation of the protein aggregates that characterize Alzheimer's and Parkinson's disease (1R21AG070374-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10107351. Licensed CC0.

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