# Spatial and temporal brain biodistribution of neuropathogenic sphingolipids of Krabbe disease

## TL;DR

The study maps the brain distribution of harmful lipids in Krabbe disease, a genetic disorder causing myelin loss, using a new imaging method.

## Contribution

A novel imaging mass spectrometry method was developed to track pathogenic glycosphingolipids in the brain of a Krabbe disease mouse model.

## Key findings

- The study reveals spatial and temporal accumulation patterns of glycosphingolipids in the murine brain.
- The method correlates lipid disturbances with myelin marker changes and astrogliosis.
- The approach can be applied to other sphingolipid-related neurodegenerative disorders.

## Abstract

Glycosphingolipids are essential lipids enriched in the outer leaflet of the plasma membrane, particularly those forming the myelin sheaths. Disorders impacting the glycosphingolipid metabolism cause devastating demyelinating diseases. We extend this observation by investigating the brain topographic pattern of the progressive accumulation of these glycosphingolipids throughout the lifespan of the murine model, correlating with alterations in myelin markers and astrogliosis. The reported IMS approach reveals disturbances in the brain glycosphingolipid spatial distribution and abundance, which is of utmost importance when examining the impact of neurotherapeutics targeting these cytotoxically elevated sphingolipids. Similar approaches can be applied to other sphingolipid-neurodegenerative disorders. The development of a novel imaging mass spectrometry (IMS) method provides key information on the spatial distribution and quantification of pathogenic glycosphingolipids, hexosphingosines, and monohexosylceramides across the brain of the murine model of Krabbe disease, an inherited lysosomal deficiency of galactocerebrosidase, associated with a demyelinating disorder with a broad spectrum of age of onset.