# Elucidating the biophysical and biological properties of the p3 fragment in Alzheimer's Disease

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2020 · $39,522

## Abstract

PROJECT SUMMARY
Alzheimer’s Disease is the 6th leading cause of death in the U.S, affecting 10% of seniors over the age of 65.
Despite the myriad Alzheimer’s Disease therapeutics targeting the production and clearance of the β-Amyloid
(Aβ) peptide, an effective cure is yet to be identified. The current, commonly accepted amyloid model of this
disease only seeks to understand the properties of two predominant isoforms of Aβ - with 40 or 42 amino acids.
However, plaques isolated from the brains of Alzheimer’s patients contain a variety of Aβ peptides and other
proteins. The long-term objective of the proposed research is to elucidate the mechanisms by which Aβ and its
variants contribute collectively to the pathology of Alzheimer’s Disease. A C-terminal fragment of Aβ, p3, has
been described as soluble and void of amyloidogenic properties since its discovery, despite minimal scientific
evidence to support this. I propose to synthesize and characterize the aggregation and mechanism of toxicity of
p3 to elucidate its role in amyloid fibril formation. My hypothesis is that the p3 fragment forms amyloid fibrils
capable of imparting drastic changes on the oligomerization of the well-studied 40 and 42 length Aβ. The current
amyloid model can be significantly improved by understanding the collective contribution of all Aβ peptides
through their kinetic interactions. Aim I will provide insights on how p3 aggregates into amyloid fibrils and how
that pathway deviates from Aβ with the use of kinetic assays, antibodies and photo-induced crosslinking. Aim 2
will create a more heterogenous model for the aggregation of amyloid peptides into fibrils through coincubation
and seeding assays with p3 and Aβ. Aim 3 will provide advances in our understanding of how p3 exerts its
toxicity on cells and how that pathway differs from that of Aβ. The mechanism of p3 toxicity will be explored with
various biorthogonal cellular uptake methods and apoptosis assays. Completing the listed aims will elucidate the
role that p3 plays in the kinetics of amyloid plaque formation and cell toxicity. By providing key insights into the
aggregation properties and biological activity of p3, the proposed work will clarify how p3 interacts with Aβ.
Ultimately, I expect the results to modify and refine the currently accepted amyloid model, providing a
more comprehensive understanding of the pathology of Alzheimer’s Disease.

## Key facts

- **NIH application ID:** 10065425
- **Project number:** 5F31AG066377-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Ariel Jade Kuhn
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,522
- **Award type:** 5
- **Project period:** 2019-09-26 → 2022-09-25

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065425

## Citation

> US National Institutes of Health, RePORTER application 10065425, Elucidating the biophysical and biological properties of the p3 fragment in Alzheimer's Disease (5F31AG066377-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10065425. Licensed CC0.

---

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