Annals of NeurologyGenetic & Genomic MedicinePeer-reviewed journal article
Plasma glucosylceramide levels are regulated by ATP10D and are not involved in Parkinson's disease pathogenesis.
Emma N. SomervilleiD, Alva James, Christian BeetziD, Robert Schwieger, Gal Barrel, Krishna Kumar Kandaswamy, Marius I. IurascuiD, Peter O. BaueriD, Michael TaiD, Hirotaka IwakiiD, Konstantin A. SenkevichiD, Eric YuiD, Roy N. AlcalayiD, Ziv Gan‐OriD
Abstract
GBA1 variants and decreased glucocerebrosidase (GCase) activity are implicated in Parkinsons disease (PD). We investigated the hypothesis that increased levels of glucosylceramide (GlcCer), one of GCase main substrates, are involved in PD pathogenesis. Using multiple genetic methods, we show that ATP10D, not GBA1, is the main regulator of plasma GlcCer levels, yet it is not involved in PD pathogenesis. Plasma GlcCer levels were associated with PD, but not in a causative manner, and are not predictive of disease status. These results argue against targeting GlcCer in GBA1-PD and underscore the need to explore alternative mechanisms and biomarkers for PD.
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