The 12 June 2023 issue of Movement Disorders marked the publication of the first research paper written as the result of the Neuropathology of Neuroacanthocytosis project at the Icahn School of Medicine at Mount Sinai. Titled "Sphingolipid and Phospholipid Levels Are Altered in Human Brain in Chorea-Acanthocytosis," Gabriel Miltenberger-Miltényi and his team  presented the first evidence of altered sphingolipid and phosholipid levels in the brains of patients with chorea-acanthocytosis (VPS13A).  From the abstract:

Background

Chorea-acanthocytosis (ChAc) is associated with mutations of VPS13A, which encodes for chorein, a protein implicated in lipid transport at intracellular membrane contact sites.

Objectives

The goal of this study was to establish the lipidomic profile of patients with ChAc.

Methods

We analyzed 593 lipid species in the caudate nucleus (CN), putamen, and dorsolateral prefrontal cortex (DLPFC) from postmortem tissues of four patients with ChAc and six patients without ChAc.

Results

We found increased levels of bis(monoacylglycerol)phosphate, sulfatide, lysophosphatidylserine, and phosphatidylcholine ether in the CN and putamen, but not in the DLPFC, of patients with ChAc. Phosphatidylserine and monoacylglycerol were increased in the CN and N-acyl phosphatidylserine in the putamen. N-acyl serine was decreased in the CN and DLPFC, whereas lysophosphatidylinositol was decreased in the DLPFC.

Conclusions

We present the first evidence of altered sphingolipid and phospholipid levels in the brains of patients with ChAc. Our observations are congruent with recent findings in cellular and animal models, and implicate defects of lipid processing in VPS13A disease pathophysiology.

The full article may be accessed at: https://doi.org/10.1002/mds.29445