# Christianson Syndrome: a novel endosomal disorder with neurodegeneration

> **NIH NIH F32** · BROWN UNIVERSITY · 2020 · $65,310

## Abstract

PROJECT SUMMARY/ABSTRACT
Defects in endo-lysosomal system are common mechanisms in neurodegenerative diseases. Elucidating key
functions of endosomal proteins will provide crucial insight into the neurodegenerative pathologies such as
Alzheimer’s disease (AD) and AD-related dementias (AD/ADRD). The goal of this research is to define cellular
mechanism mediated by the endosomal Na+/H+ exchanger 6 (NHE6) protein in aging process and
neurodegenerative diseases in our novel NHE6-null rat model. Loss-of-function mutations in NHE6 cause
Christianson syndrome (CS) in males, involving neurodevelopmental and neurodegenerative pathologies. NHE6
mutations are being actively studied in AD/ADRD pathologies, including as they may relate to pathological tau
deposition in aging. However, a hindrance in this field is that mouse models do not recapitulate key
neurodegenerative pathologies, including tau pathology. To overcome this, we generated a new NHE6-null rat
model. Rats are genetically and physiologically closer to human than mice. Importantly, the rat model improves
on current mouse models by manifesting endogenous defects of tau processing. Our specific aims are: 1)
Demonstrate neurodegeneration and tau pathology in the novel aging CS rat model; 2) Determine the
mechanisms whereby loss of NHE6 function disrupts late endosome maturation, resulting in aberrant retrograde
axonal transport. We take multidisciplinary approaches such as biochemical methods and super-resolution
imaging techniques. The proposed work will provide better understanding of mechanisms that may become a
therapeutic target for AD/ADRD.

## Key facts

- **NIH application ID:** 10022090
- **Project number:** 5F32AG066372-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Eugene Y Lee
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 5
- **Project period:** 2019-09-30 → 2022-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022090

## Citation

> US National Institutes of Health, RePORTER application 10022090, Christianson Syndrome: a novel endosomal disorder with neurodegeneration (5F32AG066372-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10022090. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*