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Funded Studies

CSF Lysosomal Hydrolases' Activity as Possible Marker of Parkinson's Disease

Objective/Rationale
Recent studies have linked lysosomal dysfunction to the accumulation of alpha-synuclein oligomers and alpha-synuclein-mediated cell death. Clinical, neuropathological and genetic associations between Gaucher’s disease, a lysosomal storage disease, and Parkison’s disease (PD) have been reported. Furthermore, a reduction of the activities of beta-glucocerebrosidase, alpha?? and beta-mannosidase has been reported in CSF of PD patients.

Project Description
De-novo and treated patients referring to the Section of Neurology, University of Perugia, Italy, will be included in the study. CSF samples will be collected from patients with PD (n=80)  and healthy subjects (n=50). Lysosomal enzyme activities (beta-glucocerebrosidase, alpha-mannosidase, beta-mannosidase, beta-hexosaminidase, beta-galactosidase, alpha-fucosidase, arylsulfatase A, arylsulfatase B, cathepsin D, and cathepsin S) will be determined in CSF samples using specific fluorimetric substrates.
The levels of monomeric and oligomeric alpha-synuclein, using a sensitive and specific ELISA method able to reveal levels as low as 1 pg/mL in human biological fluids, including plasma and CSF, will be also evaluated. Statistical analysis will be carried out using the Analyse-it (Analyse-it Software). Correlation analysis (Spearman’s rho coefficient) between lysosomal enzyme activity and alpha-synuclein will be also carried out.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:  
To date there is no accepted diagnostic test for Parkinson’s disease based on biochemical analysis of blood or cerebrospinal fluid (CSF). The potential use of CSF lysosomal enzyme activities as a diagnostic indicator, or as a marker of disease progression in PD, will be investigated. Moreover, the CSF levels of alpha-synuclein – a candidate diagnostic biomarker of PD – will be combined with the lysosomal enzyme activities in order to verify if there is any association between these biochemical parameters.

Anticipated Outcome
(i) to verify if changes in the activities of a large number of lysosomal enzymes in CSF of PD patients can be considered a diagnostic biomarker of the disease or a marker of disease progression; (ii) to confirm the specific behavior of CSF beta-glucocerebrosidase activity in PD patients; (iii) to evaluate the added value of determining also the levels of CSF alpha-synuclein.
 


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