# Alpha-synculein/tau coupling in Alzheimer's disease

> **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2020 · $422,892

## Abstract

Project Summary
Mixed neuropathologies are the most common cause of the clinical syndrome of dementia, including Alzheimer’s
disease (AD) dementia, and are also common among persons with mild cognitive impairment, the prodromal
stage of AD. Exploiting novel constitutive and conditional knockout lines as well as transgenic mouse lines, we
now propose bidirectional genetic effort designed to uncover key knowledge gaps linking alpha-synuclein (αSyn)
and tau coupling, and their relationships to synaptic and cognitive function. Leveraging emerging evidence from
independent groups including our own, we will test the central hypothesis that αSyn modulates tau pathology
and tau-associated cognitive and synaptic deficits. In the light of novel findings reported in the preliminary results,
we will i) test the prediction that constitutive ablation of the SNCA gene encoding αSyn alleviates tau pathology
and tau-induced cognitive deficits in a model of tauopathy and ii) test the hypothesis that overexpression of
human wild-type αSyn exacerbates tau pathology and tau-induced cognitive deficits in a model of tauopathy,
thereby providing a preclinical proof-of-principle that targeting this αSyn/tau coupling might be therapeutically
beneficial.

## Key facts

- **NIH application ID:** 9876038
- **Project number:** 1R21AG065693-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Sylvain E. Lesne
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $422,892
- **Award type:** 1
- **Project period:** 2020-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876038

## Citation

> US National Institutes of Health, RePORTER application 9876038, Alpha-synculein/tau coupling in Alzheimer's disease (1R21AG065693-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9876038. Licensed CC0.

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