An improved Glucocerebrosidase Assay for Accurate Prediction of Lysosomal Dysfunction: Exemplified by Its Relevance in Parkinson’s Disease

Functional lysosomes are crucial for preventing the abnormal accumulation of proteins and resulting neuronal injury and cell death associated with ageing. Given the importance of lysosomal dysfunction in neurodegenerative diseases, there is a need to develop minimally invasive methods to assess this dysfunction. Here, we describe a modified lysosomal glucocerebrosidase (GCase) assay using leukocytes isolated from human subjects, by incorporating a specific GCase inhibitor, which improved the assay by alleviating any non-specific interference. The assay was carried out using samples from both patients with Parkinson’s disease (PD) and healthy controls. GBA1 gene sequencing was performed in those whose activity was below the mean normal GCase value. PD patients showed a decreased GCase activity (3.32 ± 1.85 nmol/10⁷ WBCs/h) compared to controls (3.60 ± 2.22 nmol/10⁷ WBCs/h) in the absence of any GBA1 mutations. The results presented in this study highlight the significance of measuring the GCase activity in PD, both in individuals with GBA mutations and those without. Further, this simple and specific assay could be useful in assessing lysosomal function in the setting of any age-associated neurodegenerative diseases.