To estimate LAMP2 (lysosomal membrane-associated receptors-2) mRNA level in CD45+ peripheral blood cells of Parkinson's disease patients associated with mutations in the GBA gene (GBA-PD), non-manifesting GBA carriers (GBA-carriers), PD patients with no family history of the disease (sPD) and individuals without neurological disorders (controls).

Mutations in the GBA gene encoding the lysosomal enzyme glucocerebrosidase are the most common genetic risk factor for PD. The molecular triggers of GBA-PD remain unknown. We suggest that the dysfunction of lysosomal membrane proteins involved in autophagy can contribute to the development of PD among carriers of GBA mutations.

The study included 7 patients with GBA-PD (4 female, mean age: 61,7±13,7 y.o., mean age at onset: 58,5±11,8 y.o.), 10 GBA-Carriers (5 female,  mean age: 49,6±11,7 y.o.), 31 PD patients (17 female, mean age: 64,3±9,9 y.o., mean age at onset: 61,0±10,3 y.o.) and  43 controls (21 female, mean age: 64,2±10,1 y.o). Mononuclear CD45+ blood cells were immunomagnetically selected by magnetic cell sorting (MACS) system (Miltenyi Biotec). LAMP2 gene expression was analyzed by real-time PCR with TaqMan assay. LAMP2 expression level was normalized to the genes encoding GNB2L1 and Beta-Actin. Data values presented as median (min-max).

LAMP2 gene expression was significant decreased in GBA-PD patients 0.17(0.05-0.54) and GBA-carriers 0,47(0,25-1,61) compared to both controls 1,36 (0,12-21.49) (p=0.0002, p=0.029, respectively) and PD patients 1.20 (0,02-4,42) (p<0.0001, p=0.021, respectively). Moreover LAMP2 mRNA levels were lower in GBA-PD patients than in GBA-carriers(p=0.031). There was no significant difference between LAMP2 mRNA levels between PD patients and contols(p>0,05).

This is the first study estimating LAMP2 mRNA levels in CD45+ blood cells in GBA-PD patients and GBA-Carriers. More pronounced decrease of LAMP2 mRNA levels in GBA-PD patients compared to GBA-Carriers may suggest the role of LAMP2 as a modifier of GBA-PD. 

 The study was supported by the Russian Science Foundation grant No. 19-15-00315