Jasmin Galper1, Manisha Balwani2, Stanley Fahn3, Cheryl Waters3, Lynne Krohn4,5, Ziv Gan-Or4,5,6, Nicolas Dzamko1, Roy N Alcalay3. 1. Brain and Mind Centre and Faculty of Medicine and Health, School of Medical Sciences, University of Sydney, Camperdown, New South Wales, Australia. 2. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 3. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA. 4. Department of Human Genetics, McGill University, Montreal, Quebec, Canada. 5. The Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. 6. Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Abstract
BACKGROUND: Homozygous and compound heterozygous variants in glucocerebrosidase (GBA) can cause Gaucher disease (GD), whereas heterozygous variants increase the risk of developing Parkinson's disease (PD). GD patients display altered peripheral immune proteins. However, it is unknown if these are altered in GBA carriers with PD. OBJECTIVES: To determine whether plasma cytokines and immune biomarkers associated with GD are also altered in GBA carriers with or without PD. METHODS: Inflammatory cytokines and established GD biomarkers, ferritin, CD162, CCL18, and chitotriosidase (28 biomarkers) were measured in GBA pathogenic variant carriers with (n = 135) and without (n = 83) PD, and non-carriers with (n = 75) and without PD (n = 77). RESULTS: PD patients with biallelic pathogenic variants in GBA had elevated plasma levels of ferritin, CCL18, and MIP1α. These biomarkers were not elevated in heterozygous GBA carriers. CONCLUSION: GD plasma biomarkers are not promising candidates for stratifying the risk for PD in carriers of heterozygous GBA pathogenic variants.
BACKGROUND: Homozygous and compound heterozygous variants in glucocerebrosidase (GBA) can cause Gaucher disease (GD), whereas heterozygous variants increase the risk of developing Parkinson's disease (PD). GDpatients display altered peripheral immune proteins. However, it is unknown if these are altered in GBA carriers with PD. OBJECTIVES: To determine whether plasma cytokines and immune biomarkers associated with GD are also altered in GBA carriers with or without PD. METHODS: Inflammatory cytokines and established GD biomarkers, ferritin, CD162, CCL18, and chitotriosidase (28 biomarkers) were measured in GBA pathogenic variant carriers with (n = 135) and without (n = 83) PD, and non-carriers with (n = 75) and without PD (n = 77). RESULTS:PDpatients with biallelic pathogenic variants in GBA had elevated plasma levels of ferritin, CCL18, and MIP1α. These biomarkers were not elevated in heterozygous GBA carriers. CONCLUSION:GD plasma biomarkers are not promising candidates for stratifying the risk for PD in carriers of heterozygous GBA pathogenic variants.