Funding agencies: This work was supported by the Dutch Parkinson Foundation (Parkinson Vereniging), Neuroscience Campus Amsterdam, VU University Medical Center and the Michael J. Fox Foundation (MJFF).
Changes in endolysosomal enzyme activities in cerebrospinal fluid of patients with Parkinson's disease
Article first published online: 27 MAY 2013
Copyright © 2013 Movement Disorder Society
Volume 28, Issue 6, pages 747–754, June 2013
How to Cite
van Dijk, K. D., Persichetti, E., Chiasserini, D., Eusebi, P., Beccari, T., Calabresi, P., Berendse, H. W., Parnetti, L. and van de Berg, W. D. J. (2013), Changes in endolysosomal enzyme activities in cerebrospinal fluid of patients with Parkinson's disease. Mov. Disord., 28: 747–754. doi: 10.1002/mds.25495
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue published online: 25 JUN 2013
- Article first published online: 27 MAY 2013
- Manuscript Accepted: 3 APR 2013
- Manuscript Revised: 24 MAR 2013
- Manuscript Received: 14 SEP 2012
- enzyme activity;
- cerebrospinal fluid;
- Parkinson's disease
Parkinson's disease (PD) is characterized neuropathologically by the cytoplasmic accumulation of misfolded α-synuclein in specific brain regions. The endolysosomal pathway appears to be involved in α-synuclein degradation and, thus, may be relevant to PD pathogenesis. This assumption is further strengthened by the association between PD and mutations in the gene encoding for the lysosomal hydrolase glucocerebrosidase. The objective of the present study was to determine whether endolysosomal enzyme activities in cerebrospinal fluid (CSF) differ between PD patients and healthy controls. Activity levels of 6 lysosomal enzymes (β-hexosaminidase, α-fucosidase, β-mannosidase, β-galactosidase, β-glucocerebrosidase, and cathepsin D) and 1 endosomal enzyme (cathepsin E) were measured in CSF from 58 patients with PD (Hoehn and Yahr stages 1–3) and 52 age-matched healthy controls. Enzyme activity levels were normalized against total protein levels. Normalized cathepsin E and β-galactosidase activity levels were significantly higher in PD patients compared with controls, whereas normalized α-fucosidase activity was reduced. Other endolysosomal enzyme activity levels, including β-glucocerebrosidase activity, did not differ significantly between PD patients and controls. A combination of normalized α-fucosidase and β-galactosidase discriminated best between PD patients and controls with sensitivity and specificity values of 63%. In conclusion, the activity of a number of endolysosomal enzymes is changed in CSF from PD patients compared with healthy controls, supporting the alleged role of the endolysosomal pathway in PD pathogenesis. The usefulness of CSF endolysosomal enzyme activity levels as PD biomarkers, either alone or in combination with other markers, remains to be established in future studies. © 2013 Movement Disorder Society