# Acid Ceramidase in Alzheimers Disease

> **NIH NIH R03** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $75,500

## Abstract

PROJECT SUMMARY
The neurodegenerative condition known as Alzheimer’s disease (AD) is increasingly placing a burden on our
health care system, patients, and their families. One factor that appears to contribute to neurodegeneration, and
distinguishes the development of AD from normal ageing, is cellular senescence. However, the mechanisms,
causes and consequences of cellular senescence in AD and associated neuropathology remain poorly
understood. A recent study demonstrated a role for the lysosomal sphingolipid enzyme acid ceramidase (AC) in
ageing and senescence. Deregulation of sphingolipid metabolism has been documented in AD pathology, but
the role of AC has not been explored in animal models. Depending on pH, AC catalyzes either forward or reverse
reaction. Because primary lysosomal dysfunction and acidification impairment occurs AD, the increased pH
potentially promotes the reverse activity of AC, which would increase the stress lipid ceramide and promote
neuronal dysfunction. In this project we will test the hypothesis that acid ceramidase contributes to
neurodegeneration associated with Alzheimer’s Disease. In specific aim 1, we will generate PDAPP and 5xFAD
AD mice in which AC is deleted either in a neuron-specific or globally inducible manner. In specific Aim 2, we
will determine how loss of AC function affects AD pathology and behavior in PDAPP and 5xFAD models. The
use of neuron-specific and global AC deficient AD models will elucidate the role of the enzyme in neuronal cells
and clarify how loss of AC in other cells contributes to the disease. Understanding the role of AC in AD has the
potential for development of novel therapeutic strategies that combat this debilitating and costly disease.

## Key facts

- **NIH application ID:** 10885070
- **Project number:** 5R03AG081914-02
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** CHRISTINA VOELKEL-JOHNSON
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $75,500
- **Award type:** 5
- **Project period:** 2023-07-15 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885070

## Citation

> US National Institutes of Health, RePORTER application 10885070, Acid Ceramidase in Alzheimers Disease (5R03AG081914-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10885070. Licensed CC0.

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