# Mechanisms of spreading proteinopathy in Lewy Body Dementia

> **NIH NIH RF1** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $1,512,234

## Abstract

PROJECT SUMMARY
One
adequately
alpha-synuclein
diagnosis,
as
pathology
major obstacle to alting neurodegeneration i n Lewy body dementias is a lack of mammalian models that
display the range of neuropathological changes found in the human disease. Although aggregated
Lewy pathology occurring within specific neurons in the cortex i s required to make this
in the vast majority of cases, there is coexistent beta-amyloid plaque pathology in the same regions
Lewy pathology. The relevance these multiple proteinopathies to the formation and spread of Lewy
throughout the nervous system is currently unknown. The
h
Unni lab has been working for many years
to understand the role of cortical alpha-synuclein pathology in synucleinopathies, including pioneering in vivo
multiphoton imaging approaches that can measure the formation and spread of Lewy pathology and the
longitudinal cell fates of individual neurons with and without Lewy inclusions over a period of many months.
Recently, we and our collaborator Randall Woltjer have discovered that the presence of beta-amyloid
pathology greatly increases the formation and/or spread of Lewy pathology in mouse cortex after seeding with
alpha-synuclein preformed fibrils. In this proposal, our team will understand how the presence of beta-amyloid
plaques and tau neurofibrillary tangles accelerate the formation and spread of alpha-synuclein Lewy pathology
throughout the nervous system, and the potentially critical role played by brain-resident immune cells,
microglia, in this process. The results of this work will push forward our ability to understand and develop new
treatments for Lewy body dementias.

## Key facts

- **NIH application ID:** 10291694
- **Project number:** 1RF1NS123457-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Vivek Unni
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,512,234
- **Award type:** 1
- **Project period:** 2021-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10291694

## Citation

> US National Institutes of Health, RePORTER application 10291694, Mechanisms of spreading proteinopathy in Lewy Body Dementia (1RF1NS123457-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10291694. Licensed CC0.

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