# Reduced allelic dosage of CLP1 attenuates cognitive dysfunction and pathological burden in transgenic mouse models of Alzheimer’s disease

> **NIH NIH R03** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $155,205

## Abstract

Project Summary/Abstract
Alzheimer’s disease (AD) is the most prevalent form of dementia in the elderly caused by complex interactions
of genetic and environmental risk factors. An estimated 130 million people will develop AD by 2050, constituting
an urgent clinical need for effective treatments and therapies to be developed. Prior therapies have focused on
resolving pathological hallmarks, such as senile plaques (Ab) and neurofibrillary tangles (tau), but have failed to
improve cognitive function in patients. The RNA kinase, CLP1, was recently found to be a genetic mediator AD.
Additionally, high mRNA levels of CLP1 correlated with poor cognitive function in patients. Our preliminary
histological analysis of brain samples from dementia patients and a mouse model of AD, with controls, found a
shared, aberrant expression pattern of CLP1 protein with disease. Together, these findings lead us to
hypothesize that CLP1 overexpression may contribute to AD pathogenesis and cognitive decline in AD.
To test this idea, we will intercross mouse models of AD with Clp1 heterozygous mutant mice and assess disease
pathology and cognitive decline during AD progression for amelioration.

## Key facts

- **NIH application ID:** 10742948
- **Project number:** 5R03AG080287-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Ashleigh E Schaffer
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $155,205
- **Award type:** 5
- **Project period:** 2022-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10742948

## Citation

> US National Institutes of Health, RePORTER application 10742948, Reduced allelic dosage of CLP1 attenuates cognitive dysfunction and pathological burden in transgenic mouse models of Alzheimer’s disease (5R03AG080287-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10742948. Licensed CC0.

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