# Single molecule kinetic studies of gamma-secretase/substrate interaction and the effects of AD-causing mutations

> **NIH NIH R21** · RENSSELAER POLYTECHNIC INSTITUTE · 2021 · $233,776

## Abstract

Project Summary
Amyloid plaque, composed of amyloid-b peptide (Ab), is a pathological hallmark of Alzheimer’s
disease (AD). g-secretase is responsible for the cleavage of C99, the C-terminal fragment of 99
residues of amyloid precursor protein (APP), to generate Ab. Previous kinetics studies of g-
secretase measured the final production of APP intracellular domain (AICD) and/or Ab.
However, the kinetics rates for individual steps of the generation of Ab from C99 are lacking.
Here we will use single molecule fluorescence studies to observe enzyme/substrate molecules
in real time, and measure the kinetics of enzyme/substrate association and cleavage in g-
secretase-mediated intramembrane proteolysis to generate Ab (Aim1), and determine how
familial AD (FAD) mutations alter the kinetics of enzyme/substrate association and cleavage in
AD (Aim2).

## Key facts

- **NIH application ID:** 10125486
- **Project number:** 1R21AG067436-01A1
- **Recipient organization:** RENSSELAER POLYTECHNIC INSTITUTE
- **Principal Investigator:** Scott Thomas Forth
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $233,776
- **Award type:** 1
- **Project period:** 2021-01-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10125486

## Citation

> US National Institutes of Health, RePORTER application 10125486, Single molecule kinetic studies of gamma-secretase/substrate interaction and the effects of AD-causing mutations (1R21AG067436-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10125486. Licensed CC0.

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