Citations 1
Brain Sphingolipid and Phospholipid Levels Are Altered in XK Disease
Miltenberger-Miltenyi, Gabriel, Laborc, Klaudia, Jones, Attila, Crary, John F. , Sanctis, Claudia De , Thörn, Emma, Chiu, Lily Yu-Chia, McQuillan, Stephanie, Farrell, Kurt , Nandakumar, Renu , Al-Sarraj, S, Dickson, Dennis, Hiller, Amie , MORGELLO, SUSAN, Sammler, Esther , Troakes, Claire, Hecke, Wim Van, Westeneng, Henk-Jan, Woltjer, Randall, Wszolek, Zbigniew K, Walker, Ruth, Jones, Attila , McQuillan, Stephanie , Farrell, Kurt , Al-Sarraj, Safa , Sammler, Esther M , Woltjer, Randall L. , Miltenberger-Miltényi, Gábriel , Conceição, Vasco A. , Thorn, Emma L , Morgello, Susan , Mühlebner, Angelika , Troakes, Claire , Hecke, Wim Van , Westeneng, Henk‐Jan , Wszołek, Zbigniew K.
Movement Disorders | March 8, 2026 | Volume: 41 | Issue: 7 | Pages: 1877-1883
Abstract Background XK disease is a multisystem neurodegenerative disorder caused by mutations in the XK gene that codes for the lipid scramblase XK. Objective The aim was to describe the lipidomic spectrum in postmortem brain tissue from XK patients. Methods We measured the levels of 593 lipid species in the caudate nucleus (CN), putamen, and dorsolateral prefrontal cortex (DLPFC) from postmortem tissues of 5 XK patients and 6 controls. Results In XK patients, we observed increased levels of triacylglycerol, monoacylglycerol, phosphatidylserine, and ceramide in the CN. Acylated phosphatidylglycerol levels were reduced in both the CN and putamen. Acyl carnitine, dihydrosphingomyelin, and monosialodihexosylganglioside were reduced, whereas N ‐acyl phosphatidylethanolamine was increased in the DLPFC. N ‐Acyl serine was reduced in all three regions. Conclusions Our findings provide initial evidence of abnormal sphingolipid and phospholipid concentrations in the brains of XK patients and may provide insights into mechanisms of neurodegeneration in this disease. © 2026 International Parkinson and Movement Disorder Society.