# Designing novel therapeutics for Alzheimer’s disease using structural studies of tau

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $42,234

## Abstract

PROJECT SUMMARY/ABSTRACT
Alzheimer's disease (AD) is a condition of aging, primarily afflicting adults 65 and older, and is the most
common cause of dementia worldwide. The histopathological hallmarks of AD are amyloid plaques and
neurofibrillary tangles (NFTs), formed by aggregation of proteins amyloid-β and tau, respectively. Studies have
shown NFT formation is correlated with brain atrophy and cognitive decline. Therefore, halting tau aggregation
at early stages to prevent disease progression is a potential therapeutic avenue for AD. Previous studies in our
group determined the micro-electron diffraction structure of 305SVQIVY310, an aggregation-prone segment of
tau. We designed a peptide-based inhibitor to target its aggregating interfaces, referred to as WIW, which has
been demonstrated to halt tau aggregation in vitro and in cell models. To transport WIW across the blood-brain
barrier (BBB), I have linked WIW to a peptide tag that enters the brain via receptor-mediated endocytosis by
binding to low-density lipoprotein receptor-related protein 1. In Aim 1, I will probe the mechanism of action of
WIW by solving a co-crystal structure of WIW with its target peptide, SVQIVY. In Aim 2, I will modify WIW to
optimize its CNS delivery and plasma stability. In Aim 3, I will determine whether WIW or an optimized analog
can inhibit tau aggregation in PS19 mice, a mouse model of tauopathy. Although WIW has been demonstrated
to halt tau aggregation in vitro and in cell models, these proposed investigations will be the first structural
characterization of the mechanism of action of WIW and the first characterization of its ability to halt tau
aggregation in vivo.

## Key facts

- **NIH application ID:** 10678341
- **Project number:** 1F30AG077832-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Hope Pan
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $42,234
- **Award type:** 1
- **Project period:** 2023-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10678341

## Citation

> US National Institutes of Health, RePORTER application 10678341, Designing novel therapeutics for Alzheimer’s disease using structural studies of tau (1F30AG077832-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10678341. Licensed CC0.

---

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