Cerebrospinal Fluid Lysosomal Enzymes and Alpha-Synuclein in Parkinson's Disease
Identifieur interne : 000644 ( Main/Exploration ); précédent : 000643; suivant : 000645Cerebrospinal Fluid Lysosomal Enzymes and Alpha-Synuclein in Parkinson's Disease
Auteurs : Lucilla Parnetti [Italie] ; Davide Chiasserini [Italie] ; Emanuele Persichetti [Italie] ; Paolo Eusebi [Italie] ; Shiji Varghese [Émirats arabes unis] ; Mohammad M. Qureshi [Émirats arabes unis] ; Andrea Dardis [Italie] ; Marta Deganuto [Italie] ; Claudia De Carlo [Italie] ; Anna Castrioto [Italie] ; Chiara Balducci [Italie] ; Silvia Paciotti [Italie] ; Nicola Tambasco [Italie] ; Bruno Bembi [Italie] ; Laura Bonanni [Italie] ; Marco Onofrj [Italie] ; Aroldo Rossi [Italie] ; Tommaso Beccari [Italie] ; Omar El-Agnaf [Émirats arabes unis, Arabie saoudite] ; Paolo Calabresi [Italie]Source :
- Movement Disorders [ 0885-3185 ] ; 2014.
English descriptors
- KwdEn :
- Adult, Aged, Female, Genotype, Glucosylceramidase (cerebrospinal fluid), Glucosylceramidase (genetics), Glycoside Hydrolases (cerebrospinal fluid), Humans, Immunoassay, Male, Middle Aged, Mutation (genetics), Parkinson Disease (cerebrospinal fluid), Parkinson Disease (genetics), Prospective Studies, alpha-Synuclein (cerebrospinal fluid), tau Proteins (cerebrospinal fluid).
- MESH :
- chemical , cerebrospinal fluid : Glucosylceramidase, Glycoside Hydrolases, alpha-Synuclein, tau Proteins.
- chemical , genetics : Glucosylceramidase.
- cerebrospinal fluid : Parkinson Disease.
- genetics : Mutation, Parkinson Disease.
- Adult, Aged, Female, Genotype, Humans, Immunoassay, Male, Middle Aged, Prospective Studies.
Abstract
To assess the discriminating power of multiple cerebrospinal fluid (CSF) biomarkers for Parkinson's disease (PD), we measured several proteins playing an important role in the disease pathogenesis. The activities of β-glucocerebrosidase and other lysosomal enzymes, together with total and oligomeric α-synuclein, and total and phosphorylated tau, were thus assessed in CSF of 71 PD patients and compared to 45 neurological controls. Activities of β-glucocerebrosidase, β-mannosidase, β-hexosaminidase, and β-galactosidase were measured with established enzymatic assays, while α-synuclein and tau biomarkers were evaluated with immunoassays. A subset of PD patients (n = 44) was also screened for mutations in the β-glucocerebrosidase-encoding gene (
Url:
DOI: 10.1002/mds.25772
PubMed: 24436092
PubMed Central: 4282452
Affiliations:
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Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Cerebrospinal Fluid Lysosomal Enzymes and Alpha-Synuclein in Parkinson's Disease</title>
<author><name sortKey="Parnetti, Lucilla" sort="Parnetti, Lucilla" uniqKey="Parnetti L" first="Lucilla" last="Parnetti">Lucilla Parnetti</name>
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<author><name sortKey="Chiasserini, Davide" sort="Chiasserini, Davide" uniqKey="Chiasserini D" first="Davide" last="Chiasserini">Davide Chiasserini</name>
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<author><name sortKey="Persichetti, Emanuele" sort="Persichetti, Emanuele" uniqKey="Persichetti E" first="Emanuele" last="Persichetti">Emanuele Persichetti</name>
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<author><name sortKey="Deganuto, Marta" sort="Deganuto, Marta" uniqKey="Deganuto M" first="Marta" last="Deganuto">Marta Deganuto</name>
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<author><name sortKey="De Carlo, Claudia" sort="De Carlo, Claudia" uniqKey="De Carlo C" first="Claudia" last="De Carlo">Claudia De Carlo</name>
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<author><name sortKey="Castrioto, Anna" sort="Castrioto, Anna" uniqKey="Castrioto A" first="Anna" last="Castrioto">Anna Castrioto</name>
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<author><name sortKey="Balducci, Chiara" sort="Balducci, Chiara" uniqKey="Balducci C" first="Chiara" last="Balducci">Chiara Balducci</name>
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<author><name sortKey="Paciotti, Silvia" sort="Paciotti, Silvia" uniqKey="Paciotti S" first="Silvia" last="Paciotti">Silvia Paciotti</name>
<affiliation wicri:level="1"><nlm:aff id="au3"><institution>Department of Economic Sciences and Food Sciences (DSEEA), Section of Food Chemistry, Biochemistry, Physiology and Nutrition, University of Perugia</institution>
<addr-line>Perugia, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
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<author><name sortKey="Tambasco, Nicola" sort="Tambasco, Nicola" uniqKey="Tambasco N" first="Nicola" last="Tambasco">Nicola Tambasco</name>
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<author><name sortKey="Bembi, Bruno" sort="Bembi, Bruno" uniqKey="Bembi B" first="Bruno" last="Bembi">Bruno Bembi</name>
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</nlm:aff>
<country xml:lang="fr">Italie</country>
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<author><name sortKey="Bonanni, Laura" sort="Bonanni, Laura" uniqKey="Bonanni L" first="Laura" last="Bonanni">Laura Bonanni</name>
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<addr-line>Chieti, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Chieti</wicri:regionArea>
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</author>
<author><name sortKey="Onofrj, Marco" sort="Onofrj, Marco" uniqKey="Onofrj M" first="Marco" last="Onofrj">Marco Onofrj</name>
<affiliation wicri:level="1"><nlm:aff id="au7"><institution>Department of Neuroscience and Imaging, University G. D'Annunzio of Chieti-Pescara</institution>
<addr-line>Chieti, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Chieti</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rossi, Aroldo" sort="Rossi, Aroldo" uniqKey="Rossi A" first="Aroldo" last="Rossi">Aroldo Rossi</name>
<affiliation wicri:level="1"><nlm:aff id="au1"><institution>Clinica Neurologica, Università degli Studi di Perugia</institution>
<addr-line>Perugia, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Perugia</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Beccari, Tommaso" sort="Beccari, Tommaso" uniqKey="Beccari T" first="Tommaso" last="Beccari">Tommaso Beccari</name>
<affiliation wicri:level="1"><nlm:aff id="au3"><institution>Department of Economic Sciences and Food Sciences (DSEEA), Section of Food Chemistry, Biochemistry, Physiology and Nutrition, University of Perugia</institution>
<addr-line>Perugia, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Perugia</wicri:regionArea>
</affiliation>
</author>
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<affiliation wicri:level="1"><nlm:aff id="au5"><institution>Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University</institution>
<addr-line>Al Ain, United Arab Emirates</addr-line>
</nlm:aff>
<country xml:lang="fr">Émirats arabes unis</country>
<wicri:regionArea>Al Ain</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="au8"><institution>Faculty of Medicine, King Abdulaziz University</institution>
<addr-line>Jeddah, Saudi Arabia</addr-line>
</nlm:aff>
<country xml:lang="fr">Arabie saoudite</country>
<wicri:regionArea>Jeddah</wicri:regionArea>
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</author>
<author><name sortKey="Calabresi, Paolo" sort="Calabresi, Paolo" uniqKey="Calabresi P" first="Paolo" last="Calabresi">Paolo Calabresi</name>
<affiliation wicri:level="1"><nlm:aff id="au1"><institution>Clinica Neurologica, Università degli Studi di Perugia</institution>
<addr-line>Perugia, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Perugia</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="au2"><institution>Fondazione S. Lucia, L'Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)</institution>
<addr-line>Rome, Italy</addr-line>
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<country xml:lang="fr">Italie</country>
<wicri:regionArea>Rome</wicri:regionArea>
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</analytic>
<series><title level="j">Movement Disorders</title>
<idno type="ISSN">0885-3185</idno>
<idno type="eISSN">1531-8257</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Female</term>
<term>Genotype</term>
<term>Glucosylceramidase (cerebrospinal fluid)</term>
<term>Glucosylceramidase (genetics)</term>
<term>Glycoside Hydrolases (cerebrospinal fluid)</term>
<term>Humans</term>
<term>Immunoassay</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Mutation (genetics)</term>
<term>Parkinson Disease (cerebrospinal fluid)</term>
<term>Parkinson Disease (genetics)</term>
<term>Prospective Studies</term>
<term>alpha-Synuclein (cerebrospinal fluid)</term>
<term>tau Proteins (cerebrospinal fluid)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="cerebrospinal fluid" xml:lang="en"><term>Glucosylceramidase</term>
<term>Glycoside Hydrolases</term>
<term>alpha-Synuclein</term>
<term>tau Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Glucosylceramidase</term>
</keywords>
<keywords scheme="MESH" qualifier="cerebrospinal fluid" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Mutation</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Female</term>
<term>Genotype</term>
<term>Humans</term>
<term>Immunoassay</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Prospective Studies</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>To assess the discriminating power of multiple cerebrospinal fluid (CSF) biomarkers for Parkinson's disease (PD), we measured several proteins playing an important role in the disease pathogenesis. The activities of β-glucocerebrosidase and other lysosomal enzymes, together with total and oligomeric α-synuclein, and total and phosphorylated tau, were thus assessed in CSF of 71 PD patients and compared to 45 neurological controls. Activities of β-glucocerebrosidase, β-mannosidase, β-hexosaminidase, and β-galactosidase were measured with established enzymatic assays, while α-synuclein and tau biomarkers were evaluated with immunoassays. A subset of PD patients (n = 44) was also screened for mutations in the β-glucocerebrosidase-encoding gene (<italic>GBA1</italic>
). In the PD group, β-glucocerebrosidase activity was reduced (<italic>P</italic>
< 0.05) and patients at earlier stages showed lower enzymatic activity (<italic>P</italic>
< 0.05); conversely, β-hexosaminidase activity was significantly increased (<italic>P</italic>
< 0.05). Eight PD patients (18%) presented <italic>GBA1</italic>
sequence variations; 3 of them were heterozygous for the N370S mutation. Levels of total α-synuclein were significantly reduced (<italic>P</italic>
< 0.05) in PD, in contrast to increased levels of α-synuclein oligomers, with a higher oligomeric/total α-synuclein ratio in PD patients when compared with controls (<italic>P</italic>
< 0.001). A combination of β-glucocerebrosidase activity, oligomeric/total α-synuclein ratio, and age gave the best performance in discriminating PD from neurological controls (sensitivity 82%; specificity 71%, area under the receiver operating characteristic curve = 0.87). These results demonstrate the possibility of detecting lysosomal dysfunction in CSF and further support the need to combine different biomarkers for improving the diagnostic accuracy of PD.</p>
</div>
</front>
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<author><name sortKey="Chahinian, H" uniqKey="Chahinian H">H Chahinian</name>
</author>
<author><name sortKey="Maresca, M" uniqKey="Maresca M">M Maresca</name>
</author>
<author><name sortKey="Taieb, N" uniqKey="Taieb N">N Taieb</name>
</author>
<author><name sortKey="Yahi, N" uniqKey="Yahi N">N Yahi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Van Dijk, Kd" uniqKey="Van Dijk K">KD van Dijk</name>
</author>
<author><name sortKey="Persichetti, E" uniqKey="Persichetti E">E Persichetti</name>
</author>
<author><name sortKey="Chiasserini, D" uniqKey="Chiasserini D">D Chiasserini</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Parnetti, L" uniqKey="Parnetti L">L Parnetti</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shi, M" uniqKey="Shi M">M Shi</name>
</author>
<author><name sortKey="Bradner, J" uniqKey="Bradner J">J Bradner</name>
</author>
<author><name sortKey="Hancock, Am" uniqKey="Hancock A">AM Hancock</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Van Dijk, Kd" uniqKey="Van Dijk K">KD van Dijk</name>
</author>
<author><name sortKey="Bidinosti, M" uniqKey="Bidinosti M">M Bidinosti</name>
</author>
<author><name sortKey="Weiss, A" uniqKey="Weiss A">A Weiss</name>
</author>
<author><name sortKey="Raijmakers, P" uniqKey="Raijmakers P">P Raijmakers</name>
</author>
<author><name sortKey="Berendse, Hw" uniqKey="Berendse H">HW Berendse</name>
</author>
<author><name sortKey="Van De Berg, Wd" uniqKey="Van De Berg W">WD van de Berg</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Arabie saoudite</li>
<li>Italie</li>
<li>Émirats arabes unis</li>
</country>
</list>
<tree><country name="Italie"><noRegion><name sortKey="Parnetti, Lucilla" sort="Parnetti, Lucilla" uniqKey="Parnetti L" first="Lucilla" last="Parnetti">Lucilla Parnetti</name>
</noRegion>
<name sortKey="Balducci, Chiara" sort="Balducci, Chiara" uniqKey="Balducci C" first="Chiara" last="Balducci">Chiara Balducci</name>
<name sortKey="Beccari, Tommaso" sort="Beccari, Tommaso" uniqKey="Beccari T" first="Tommaso" last="Beccari">Tommaso Beccari</name>
<name sortKey="Bembi, Bruno" sort="Bembi, Bruno" uniqKey="Bembi B" first="Bruno" last="Bembi">Bruno Bembi</name>
<name sortKey="Bonanni, Laura" sort="Bonanni, Laura" uniqKey="Bonanni L" first="Laura" last="Bonanni">Laura Bonanni</name>
<name sortKey="Calabresi, Paolo" sort="Calabresi, Paolo" uniqKey="Calabresi P" first="Paolo" last="Calabresi">Paolo Calabresi</name>
<name sortKey="Calabresi, Paolo" sort="Calabresi, Paolo" uniqKey="Calabresi P" first="Paolo" last="Calabresi">Paolo Calabresi</name>
<name sortKey="Castrioto, Anna" sort="Castrioto, Anna" uniqKey="Castrioto A" first="Anna" last="Castrioto">Anna Castrioto</name>
<name sortKey="Chiasserini, Davide" sort="Chiasserini, Davide" uniqKey="Chiasserini D" first="Davide" last="Chiasserini">Davide Chiasserini</name>
<name sortKey="Chiasserini, Davide" sort="Chiasserini, Davide" uniqKey="Chiasserini D" first="Davide" last="Chiasserini">Davide Chiasserini</name>
<name sortKey="Dardis, Andrea" sort="Dardis, Andrea" uniqKey="Dardis A" first="Andrea" last="Dardis">Andrea Dardis</name>
<name sortKey="De Carlo, Claudia" sort="De Carlo, Claudia" uniqKey="De Carlo C" first="Claudia" last="De Carlo">Claudia De Carlo</name>
<name sortKey="Deganuto, Marta" sort="Deganuto, Marta" uniqKey="Deganuto M" first="Marta" last="Deganuto">Marta Deganuto</name>
<name sortKey="Eusebi, Paolo" sort="Eusebi, Paolo" uniqKey="Eusebi P" first="Paolo" last="Eusebi">Paolo Eusebi</name>
<name sortKey="Onofrj, Marco" sort="Onofrj, Marco" uniqKey="Onofrj M" first="Marco" last="Onofrj">Marco Onofrj</name>
<name sortKey="Paciotti, Silvia" sort="Paciotti, Silvia" uniqKey="Paciotti S" first="Silvia" last="Paciotti">Silvia Paciotti</name>
<name sortKey="Persichetti, Emanuele" sort="Persichetti, Emanuele" uniqKey="Persichetti E" first="Emanuele" last="Persichetti">Emanuele Persichetti</name>
<name sortKey="Rossi, Aroldo" sort="Rossi, Aroldo" uniqKey="Rossi A" first="Aroldo" last="Rossi">Aroldo Rossi</name>
<name sortKey="Tambasco, Nicola" sort="Tambasco, Nicola" uniqKey="Tambasco N" first="Nicola" last="Tambasco">Nicola Tambasco</name>
</country>
<country name="Émirats arabes unis"><noRegion><name sortKey="Varghese, Shiji" sort="Varghese, Shiji" uniqKey="Varghese S" first="Shiji" last="Varghese">Shiji Varghese</name>
</noRegion>
<name sortKey="El Agnaf, Omar" sort="El Agnaf, Omar" uniqKey="El Agnaf O" first="Omar" last="El-Agnaf">Omar El-Agnaf</name>
<name sortKey="Qureshi, Mohammad M" sort="Qureshi, Mohammad M" uniqKey="Qureshi M" first="Mohammad M" last="Qureshi">Mohammad M. Qureshi</name>
</country>
<country name="Arabie saoudite"><noRegion><name sortKey="El Agnaf, Omar" sort="El Agnaf, Omar" uniqKey="El Agnaf O" first="Omar" last="El-Agnaf">Omar El-Agnaf</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>
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