Peripheral ß-glucocerebrosidase enzyme activity and lipidomics in ß-glucocerebrosidase (GBA1) mutation Parkinson disease (P2.149)

• DOI: 10.1212/wnl.84.14_supplement.p2.149
• Publication Date: 2023-12-06T23:42:28Z
• Authors: Amanda Glickman; Olaf Bodamer; Britt Johnson; William Nichols; Mariel Pullman; Robert Ortega; Brooke Johannes; Deborah Raymond; Laurie Ozelius; Jacek Bielawski; Susan Bressman; Lina Obeid; Yusuf Hannun; Rachel Saunders-P...

OBJECTIVE: To determine whether peripheral s-glucocerebrosidase (GCase) enzyme activity and lipid levels are potential markers for GBA1 mutation Parkinson disease (GBA-PD). BACKGROUND: Mutations in GBA1, which encodes lysosomal GCase, lead to increased glycolipids biallelic Gaucher risk of (PD) the heterozygous form. The relationship between GCase activity, clinical outcomes could identify pharmacodynamic GBA-PD elucidate etiology. DESIGN/METHODS: Sera high level lipidomics dried blood spots (DBS) were collected from 15 PD with one 8 major Ashkenazi Jewish mutations (GBA-PD), 13 non-GBA idiopathic (IPD) 5 non-GBA, non-PD controls. Major sphingolipids built on C18:1 C18:0 sphingoid bases, base phosphates, molecular species ceramide, hexosylceramides, lactosylceramides analyzed by tandem HPLC-Mass spectrometry (MS/MS). was assessed DBS using mass spectroscopy. GBA-PD, IPD controls compared Mann-Whitney. Generalized linear models also tested. RESULTS: The mean prominent brain lipids hexosylceramide, C18 sphingosine (3.4±5.3, 6.4±2.8, 3.4±2.9 pmol/mL) (0.2±0.1, 3.8±0.6, 0.8±0.3) (p=0.02, p=0.01, p<0.01) (0.2±0.04, 4.3±1.3, 1.5±1.0) p<0.01). significantly decreased (3.49±2.81 μmol/L/h) (6.13±1.26) (p=0.04) (7.05±4.94) (p=0.03). While overall did not differ controls, a subset had glycolipid abnormal ranges. CONCLUSIONS: Increased suggest disruption enzymatic pathway indicate markers. Increases specifically further support possibility shared pathophysiology disease, IPD. Study Supported by: NIH K02NS073836, Marcled Foundation, Bigglesworth Foundation Disclosure: Dr. Glickman has nothing disclose. Bodamer Johnson Nichols Pullman Ortega Johannes Raymond Ozelius disclose., Bielawski Bressman Obeid Hannun Saunders-Pullman