# Presenilin Knock-in Rat Model of Neurodegeneration

> **NIH NIH R00** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $249,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Alzheimer's disease (AD) is the most common form of dementia in the elderly, and currently there exists no
disease modifying therapy. Familial forms of AD (FAD) are caused by mutations in Amyloid Precursor Protein
(APP), whose processing can result in the formation of amyloid beta (Aβ), or by mutations in Presenilin 1/2
(PSEN1/2), which comprise in part the γ-secretase complex that cleaves Aβ from fragments of APP. My long-
term career goal is to study the mechanism of neurodegeneration in Alzheimer disease. The more proximate
goal, as put forward in this proposal, is to characterize the neurodegeneration in a new rat knock-in model of
Presenilin1 dysfunction. Psen1-knockout (Psen1-KO) mice and knock-in (KI) mice with homozygous FAD-
associated L435F mutations (Psen1LF/LF) are embryonic and perinatally lethal, precluding a more rigorous
examination of the effect of AD-causing Psen1 mutations on neurodegeneration. Given the better suitability of
rats as a model organism, with regards to surgical interventions and behavior testing, we generated a rat KI
model of the Psen1LF mutation. We find that, unexpectedly and in contrast to Psen1LF/LF, Psen1LF/LF rats survive
into adulthood despite a loss of γ-secretase activity. The survival of these rats affords the opportunity to
examine the effect of homozygous Psen1 AD mutations on neurodegeneration.

## Key facts

- **NIH application ID:** 10782011
- **Project number:** 5R00AG065441-04
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** MARC D TAMBINI
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2021-05-15 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10782011

## Citation

> US National Institutes of Health, RePORTER application 10782011, Presenilin Knock-in Rat Model of Neurodegeneration (5R00AG065441-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10782011. Licensed CC0.

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