# Modeling Lewy body dementia  in vivo: Towards a better understanding of alpha synuclein and Tau interaction in disease

> **NIH NIH R03** · MAYO CLINIC  JACKSONVILLE · 2020 · $156,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Lewy body dementia (LBD) is a term used to encompass both Parkinson’s disease dementia (PDD) and
dementia with Lewy body (DLB) disorders. They are the second most common type of dementia after
Alzheimer’s disease but are yet often misdiagnosed. Indeed, LBD appears to fall somewhere in the middle of a
disease spectrum ranging from Alzheimer’s to Parkinson’s disease. Despite abundant evidence of a central
role for alpha-synuclein (αsyn) in LBD pathogenesis, evidence shows that tau lesions, such as hyper
phosphorylated tau protein, often coexists in DLB and PDD brains. Comorbid αsyn and tau pathology may be
critical for the formation of disease-specific pathogenic aggregates that determine susceptibility to developing
disease. Post-mortem brain investigations have reported presence of tau oligomers colocalizing with αsyn
oligomers and in vitro and in vivo studies demonstrated that αsyn and tau promote the fibrilization of one
another. Yet, a major unanswered question in the field is what mechanisms underlie LBD and how αsyn/tau
interplay influences neurodegenerative processes.
Rodent models continue to play a key role in advancing our understanding of neurodegenerative disorders and
are a valuable tool to decipher mechanism of diseases. Development of models recapitulating the comorbid
pathology and differential clinical symptom onset of PDD and DLB will help the field to better understand LBD
pathogenesis and the cellular mechanisms that lead to neurodegeneration. Herein, we propose to identify the
role of in-vivo αsyn/tau crosstalk and help to elucidate how tau and αsyn exert their toxicity in de novo mouse
models where temporally controlled co-pathology will be induced. Indeed we will use AAV vector technology to
transduce tau or αsyn expression in the adult brain of transgenic animals already presenting or αsyn or tau
pathology respectively. Overall, the objective is to identify if αsyn and tau interplay results in enhanced
pathology and dysfunction in these two different animal models. To answer these questions behavioral,
histological and biochemical analyses will be conducted. These approaches will yield important insight into
αsyn/tau interaction in vivo and may have the potential to model PDD and DLB pathology independently.

## Key facts

- **NIH application ID:** 9975335
- **Project number:** 1R03NS112611-01A1
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** Marion Delenclos
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $156,500
- **Award type:** 1
- **Project period:** 2020-04-01 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975335

## Citation

> US National Institutes of Health, RePORTER application 9975335, Modeling Lewy body dementia  in vivo: Towards a better understanding of alpha synuclein and Tau interaction in disease (1R03NS112611-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9975335. Licensed CC0.

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