# Regulation of human tau expression and tauopathy by alpha-synuclein

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2022 · $764,792

## Abstract

Project Summary
Mixed neuropathologies are the most common cause of the clinical syndrome of dementia, including Alzheimer's
disease (AD), Lewy body dementia (LBD) and frontotemporal dementia (FTD). Exploiting novel constitutive and
conditional knockout lines as well as transgenic mouse lines, we now propose a series of genetic approaches
designed to uncover key knowledge gaps linking alpha-synuclein (αSyn) and tau biology, pathologies 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 expression, independent of αSyn pathology, may
impact the biology tau and/or tau-dependent pathology. In the light of novel findings reported in the preliminary
results, we will i) test the hypothesis that αSyn regulates human tau selectively, but not mouse tau, ii) 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, iii) test the hypothesis that conditional ablation of SNCA in forebrain
excitatory neurons alleviates 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
in the context of FTD and LBD.

## Key facts

- **NIH application ID:** 10464632
- **Project number:** 1R01AG077743-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** MICHAEL K LEE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $764,792
- **Award type:** 1
- **Project period:** 2022-06-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464632

## Citation

> US National Institutes of Health, RePORTER application 10464632, Regulation of human tau expression and tauopathy by alpha-synuclein (1R01AG077743-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10464632. Licensed CC0.

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