# Dissecting the role of tau glycosylation in Alzheimer's disease

> **NIH NIH RF1** · UNIVERSITY OF COLORADO · 2023 · $2,031,054

## Abstract

Multiple neurodegenerative conditions including Alzheimer’s disease (AD) are characterized by
the accumulation of in the brain. Tau is a heavily modified protein,
and
SUMMARY.
Microtubule-Associated Protein Tau (MAPT)
specific to glycosylation, it has been found to be N-glycosylated in AD samples but not in healthy controls.
Three N-glycosylation sites were identified in hTau40, but the exact impact of glycosylation on biophysical
properties and cellular uptake is poorly understood. In this proposal, we aim to understand how the structure,
topology, and location of glycans impact biological functions of Tau. Based on the preliminary data presented in
this application, we will pursue the following three aims: In Aim 1, we will study the effects on N-glycosylation
together with other modifications modulating the phase behavior of Tau. In Aim 2, we will study synergistic and
antagonistic effects of Tau glycosylation and other posttranslational modifications. In Aim 3, we will investigate
cellular uptake, toxicity, and stability of Tau glycoproteins in hiPSC-derived neurons. Taken together, this project
will address an important knowledge gap regarding the role of glycans and enable the design of novel therapeutic
and diagnostic strategies.

## Key facts

- **NIH application ID:** 10662150
- **Project number:** 1RF1AG079294-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Maciej Walczak
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $2,031,054
- **Award type:** 1
- **Project period:** 2023-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10662150

## Citation

> US National Institutes of Health, RePORTER application 10662150, Dissecting the role of tau glycosylation in Alzheimer's disease (1RF1AG079294-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10662150. Licensed CC0.

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