# Intranasal TIDM peptide for tauopathy

> **NIH NIH R21** · RUSH UNIVERSITY MEDICAL CENTER · 2021 · $157,000

## Abstract

Effective reduction of aggregated tau from the brain parenchyma is expected to reduce the development and
progression of both sporadic and familial Alzheimer’s disease (AD), progressive supranuclear palsy (PSP),
frontotemporal dementia (FTD), and other tauopathies. However, pathways for lowering aggregated tau from
the brain are poorly understood. Neuroinflammation is another hallmark of neurodegenerative disorders and
recently it has been shown that the progression of phospho-tau pathology is driven by microglia and that
microglial activation forms the crucial link between tau aggregation and brain damage. Here, we want to test
a novel hypothesis that intranasal administration of wild type TLR2-interacting domain of MyD88
(wtTIDM) peptide suppresses microglial inflammation and decreases tauopathy in P301S transgenic mice
via TLR2. A positive outcome of this grant proposal will delineate a new crosstalk between TLR2 and
tauopathy and describe if selective targeting of activated status of TLR2 by wtTIDM peptide reduces tangle
pathology, highlighting the discovery of a prospective intranasal agent to reduce tau pathology in AD, PSP,
FTD, and other tauopathies.
Administrative supplement: TLR2 is present in different cell types in the brain. For example, in the brain, in
addition to microglia, TLR2 is also expressed in neurons. Therefore, here, we will investigate the role of
neuronal and microglial TLR2 in tauopathy and wtTIDM peptide-mediated clearance of tauopathy and
improvement in cognitive behaviors in P301S transgenic mice.

## Key facts

- **NIH application ID:** 10274908
- **Project number:** 3R21AG069229-01S1
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** KALIPADA PAHAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $157,000
- **Award type:** 3
- **Project period:** 2020-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10274908

## Citation

> US National Institutes of Health, RePORTER application 10274908, Intranasal TIDM peptide for tauopathy (3R21AG069229-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10274908. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*