# Multilineage DAmFRET to investigate AD/ADRD protein phase behavior in neural tissue models

> **NIH NIH R21** · STOWERS INSTITUTE FOR MEDICAL RESEARCH · 2024 · $206,250

## Abstract

Project Summary/Abstract
Alzheimer's Disease and Related Dementias (AD/ADRD) are the most common forms of dementia. No
treatments exist to stop or prevent them. AD/ADRD are caused in part by the aggregation of one, or more often
a combination of, specific proteins. TDP-43 is one of a handful of such proteins. It characteristically transitions
from a dynamic liquid phase of assembly to a rigid and pathogenic phase in a large fraction of dementia cases.
This transition occurs against a backdrop of progressive changes in the interactions between different cell
types in the brain. An interdependence of these molecular and cellular changes likely determines the clinical
courses of AD/ADRD, but to understand that interdependence, we need new tools with which to compare
protein phase transitions and their corresponding phenotype effects in the context of interacting brain cell
types. We propose here to develop such a tool by modifying a cell-based biophysical method, Distributed
Amphifluoric FRET (DAmFRET) for use in human induced pluripotent stem cell (hiPSC)-derived brain tissue
models (Aim 1). We will simultaneously use DAmFRET to develop TDP-43 as a reporter of cell type-specific
differences in the homeostasis of protein phase transitions (Aim 2). By completing these aims, we will have
created and validated a uniquely powerful tool for better understanding the complex molecular and cellular
causes of AD/ADRD.

## Key facts

- **NIH application ID:** 10768678
- **Project number:** 5R21AG080434-02
- **Recipient organization:** STOWERS INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Randal Arthur Halfmann
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $206,250
- **Award type:** 5
- **Project period:** 2023-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10768678

## Citation

> US National Institutes of Health, RePORTER application 10768678, Multilineage DAmFRET to investigate AD/ADRD protein phase behavior in neural tissue models (5R21AG080434-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10768678. Licensed CC0.

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