Cerebrospinal fluid β-glucocerebrosidase activity is reduced in Dementia with Lewy Bodies

Abstract

The autophagy–lysosomal degradation pathway plays a role in the onset and progression of neurodegenerative diseases. Clinical and genetic studies indicate that mutations of β-glucocerebrosidase represent genetic risk factors for synucleinopathies, including Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). We recently found a decreased activity of lysosomal hydrolases, namely β-glucocerebrosidase, in cerebrospinal fluid of PD patients. We have thus measured the activity of these enzymes – α-mannosidase (EC 3.2.1.24), β-mannosidase (EC 3.2.1.25), β-glucocerebrosidase (EC 3.2.1.45), β-galactosidase (EC 3.2.1.23) and β-hexosaminidase (EC 3.2.1.52) – in cerebrospinal fluid of patients suffering from DLB, Alzheimer's Disease (AD), Fronto-Temporal Dementia (FTD) and controls. Alpha-mannosidase activity showed a marked decrease across all the pathological groups as compared to controls. Conversely, β-glucocerebrosidase activity was selectively reduced in DLB, further suggesting that this enzyme might specifically be impaired in synucleinopathies.

Keywords

• β-glucocerebrosidase
• α-mannosidase
• Lysosomal enzymes
• Lysosomal hydrolases
• Synucleinopathies
• Cerebrospinal fluid