Plasma Glucosylceramide Levels Are Regulated by <scp><i>ATP10D</i></scp> and Are Not Involved in Parkinson's Disease Pathogenesis

GBA1 variants and decreased glucocerebrosidase activity are implicated in Parkinson's disease (PD). We investigated the hypothesis that increased levels of glucosylceramide (GlcCer), a main substrate of glucocerebrosidase, are involved in PD pathogenesis. Using multiple genetic methods, we show that ATPase phospholipid transporting 10D (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. ANN NEUROL 2025;97:873-878.

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Publication Details

Journal
Annals of Neurology
Published
2025-03-01
DOI
https://doi.org/10.1002/ana.27219
Citations
4
Primary Topic
Lysosomal Storage Disorders Research
Type
article
Field-Weighted Citation Impact
4.66

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article

Plasma Glucosylceramide Levels Are Regulated by ATP10D and Are Not Involved in Parkinson's Disease Pathogenesis

Konstantin A. Senkevich, Michael Ta, Roy N. Alcalay, Eric Yu et al.
4 citations
Annals of Neurology
Lysosomal Storage Disorders Research
4.66
article

Plasma Glucosylceramide Levels Are Regulated by ATP10D and Are Not Involved in Parkinson's Disease Pathogenesis

Konstantin A. Senkevich, Michael Ta, Roy N. Alcalay, Eric Yu, Peter Bauer, Emma N. Somerville, Christian Beetz, Krishna Kumar Kandaswamy, Ziv Gan‐Or, Hirotaka Iwaki, Gal Barrel, Robert Schwieger, Marius I. Iurascu, Alva James
article en
4 citations

Abstract

GBA1 variants and decreased glucocerebrosidase activity are implicated in Parkinson's disease (PD). We investigated the hypothesis that increased levels of glucosylceramide (GlcCer), a main substrate of glucocerebrosidase, are involved in PD pathogenesis. Using multiple genetic methods, we show that ATPase phospholipid transporting 10D (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. ANN NEUROL 2025;97:873-878.

Annals of NeurologyVol. 97(5)
Montreal Neurological Institute and Hospital (CA), National Institutes of Health (US), Tel Aviv University (IL), Columbia University Irving Medical Center (US), Tel Aviv Sourasky Medical Center (IL), Data Tecnica International (United States) (US), National Institute on Aging (US), Centogene (Germany) (DE), McGill University (CA)
Michael J. Fox Foundation for Parkinson's Research, National Institute on Aging
Openalex Percentile: Top 6%
Lysosomal Storage Disorders Research
4.66
DOIOpen Access PDFOpenAlex
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