Objective: To evaluate cerebrospinal fluid (CSF) levels of lysosomal enzymes and assess their relationship with cognition in PD as potential early biomarkers of cognitive failure.

Background: The endolysosomal pathway is involved in α-synuclein degradation. In PD cerebral spreading of α-synuclein is associated with dementia and mutations in the lysosomal enzyme glucocerebrosidase is associated with PD and is a risk factor for dementia in PD. Previous investigation has shown differences in certain CSF lysosomal enzymes between PD and controls (1).

Methods: CSF activities of the lysosomal enzymes β-Glucocerebrosidase (GCase), α-Hexosaminidase (α-Hex), α-Fucosidase (α-Fuc), β-Galactosidase (β-Gal) and Cathepsin D (CatD) were measured in 43 non-demented PD patients and 45 controls using fluorogenic substrates, according to previously published procedures (2). The protein concentration was determined using the Bradford’s method. All of the measurements were performed in triplicate. For all of the assays the acceptance specification for within-run coefficient of variation (CV) was fixed at less than 10%. Lysosomal activities were normalized for total protein concentration. Patients underwent a clinical evaluation including all UPDRS scales, and scales for neuropsychyatric symptoms (HADS and NPI) and quality of life (PDQ-39). A comprehensive neuropsychological evaluation was performed, allowing for the diagnosis of PD-MCI according to MDS Task Force (level II).

Results: There were no differences on any of the lysosomal enzyme activities between PD patients and controls. 25 PD patients met criteria for PD-MCI and 18 were cognitively normal. Lysosomal enzyme activities were not different between PD-MCI and PDCN patients and did not correlated with scores in any cognitive test or domain. In PD patients, controlling for age CatD non-normalized activity positively correlated with UPDRS I (r=0.345; p=0.024) and IV (r=0.369; p=0.011), HADS (r=0.362; p=0.007), NPI (0.428; p=0.004), and PDQ-39 (r= 0.312; p=0.034).

Conclusions: The lysosomal enzymes studied herein seem not to be associated with cognition in PD. Only high levels of CatD were associated with worse non-motor and neuropsychiatric symptoms, motor complications and quality of life.

References: 1. van Dijk KD, Persichetti E, Chiasserini D, et al. Changes in endolysosomal enzyme activities in cerebrospinal fluid of patients with Parkinson’s disease. Mov Disord. 2013 Jun;28(6):747-54.

2. Persichetti E, Chiasserini D, Parnetti L, et al. Factors influencing the measurement of lysosomal enzymes activity in human cerebrospinal fluid. PLoS One. 2014;9(7):e101453.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cerebrospinal-fluid-lysosomal-enzymes-and-cognition-in-parkinsons-disease/