Changes in endolysosomal enzyme activities in cerebrospinal fluid of patients with Parkinson's disease.
Identifieur interne : 000A75 ( Main/Exploration ); précédent : 000A74; suivant : 000A76Changes in endolysosomal enzyme activities in cerebrospinal fluid of patients with Parkinson's disease.
Auteurs : Karin D. Van Dijk [Pays-Bas] ; Emanuele Persichetti ; Davide Chiasserini ; Paolo Eusebi ; Tommaso Beccari ; Paolo Calabresi ; Henk W. Berendse ; Lucilla Parnetti ; Wilma D J. Van De BergSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2013.
English descriptors
- KwdEn :
- MESH :
- chemical , cerebrospinal fluid : Glycoside Hydrolases.
- cerebrospinal fluid : Parkinson Disease.
- enzymology : Lysosomes.
- pathology : Parkinson Disease.
- Adult, Aged, Aged, 80 and over, Case-Control Studies, Female, Humans, Male, Middle Aged.
Abstract
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.
DOI: 10.1002/mds.25495
PubMed: 23712522
Affiliations:
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Le document en format XML
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<term>Aged</term>
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<front><div type="abstract" xml:lang="en">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.</div>
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<name sortKey="Chiasserini, Davide" sort="Chiasserini, Davide" uniqKey="Chiasserini D" first="Davide" last="Chiasserini">Davide Chiasserini</name>
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<name sortKey="Parnetti, Lucilla" sort="Parnetti, Lucilla" uniqKey="Parnetti L" first="Lucilla" last="Parnetti">Lucilla Parnetti</name>
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