No Evidence That Glucosylsphingosine Is a Biomarker for Parkinson's Disease: Statistical Differences Do Not Necessarily Indicate Biological Significance

Reply to: No Evidence that Glucosylsphingosine Is a Biomarker for Parkinson Disease

“…We thank Gleason and colleagues for their valuable comments. 1 The authors reported they read with great interest our findings of elevated levels of plasma glucosylsphingosine in GBA1 N370S mutation carriers, but challenged our conclusion that plasma glucosylsphingosine may serve as a useful biomarker for GBA1-related Parkinson's disease (GBA1-PD). We stand behind our statement that plasma glucosylsphingosine may serve as a useful biomarker for GBA1-PD, and acknowledge it requires clarification, especially related to specific uses of biomarkers.…”

“…Evidence of target modulation via objective and quantitative biomarkers is critical for interpretation of efficacy results. 3 In addition to target engagement biomarkers for GBA1-PD, there is an urgent need for: (1) biomarkers that can identify asymptomatic GBA1 pathogenic variant carriers who are more likely to develop PD to conduct patient-enriched therapeutic trials, and (2) to monitor the progression of GBA1-PD compared to idiopathic PD. As stated in our manuscript, larger and longitudinal cohort studies are required to test if glucosylsphingosine is an appropriate biomarker for these objectives.…”

Could Blood Hexosylsphingosine Be a Marker for Parkinson's Disease Linked with GBA1 Mutations?

“…We read with great interest the discussion on the topic if glucosylsphingosine (GlcSph) could be viewed as a biomarker for Parkinson's (PD) disease in the carriers of the mutations in the glucocerebrosidase (GCase; GBA1) gene between Surface et al 1 and Gleason et al 2 Surface et al 1 demonstrated that a single N370S allele is sufficient to result in a significant increase of plasma GlcSph concentration compared with patients with PD without GBA1 mutations and controls independent of PD status. Based on our data, we could extend the conclusion made by Surface et al 1 to L444P heterozygotes as well.…”