{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T05:38:37Z","timestamp":1774417117392,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,5,13]],"date-time":"2015-05-13T00:00:00Z","timestamp":1431475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Spain's Ministry of Health","award":["CP09\/00102"],"award-info":[{"award-number":["CP09\/00102"]}]},{"name":"Spain's Ministry of Health","award":["PI12\/1702"],"award-info":[{"award-number":["PI12\/1702"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2015,6]]},"abstract":"Aims<\/jats:title>As cystatin C<\/jats:styled-content> (CysC<\/jats:styled-content>) is involved in some forms of neurodegeneration, we investigated the possible relationship between CysC<\/jats:styled-content> and multiple system atrophy (MSA<\/jats:styled-content>), including its parkinsonian (MSAp<\/jats:styled-content>) and cerebellar (MSAc<\/jats:styled-content>) phenotypes.<\/jats:p><\/jats:sec>Methods<\/jats:title>Cystatin C<\/jats:styled-content> gene (CST<\/jats:styled-content>3) haplotypes were determined by PCR<\/jats:styled-content> followed by KspI<\/jats:styled-content> digestion in 50 MSA<\/jats:styled-content> patients and 108 controls. CST<\/jats:styled-content>3 and cathepsins B<\/jats:styled-content>, D<\/jats:styled-content> and L<\/jats:styled-content>1 mRNA<\/jats:styled-content> levels were studied in frozen post\u2010mortem<\/jats:italic> caudate nucleus and cerebellar samples of eight MSAp<\/jats:styled-content>, four MSAc<\/jats:styled-content> and 18 control brains and analysed by the \u0394\u0394C<\/jats:styled-content>t method. CysC<\/jats:styled-content> immunohistochemistry was performed on three MSAp<\/jats:styled-content>, three MSAc<\/jats:styled-content> and three control cerebella. Additionally, determination of CST<\/jats:styled-content>3 and cathepsins B<\/jats:styled-content>, D<\/jats:styled-content> and L<\/jats:styled-content>1 mRNA<\/jats:styled-content> levels and immunohistochemistry for CysC<\/jats:styled-content> were carried out in cerebella from three patients with paraneoplastic cerebellar degeneration, three with spinocerebellar ataxia (type 3, SCA<\/jats:styled-content>3) and three with cerebellar ischaemia (CI<\/jats:styled-content>).<\/jats:p><\/jats:sec>Results<\/jats:title>In the set of blood samples, the CST<\/jats:styled-content>3 B<\/jats:styled-content>\u2010haplotype was associated with MSAp<\/jats:styled-content> (OR<\/jats:styled-content> 4.86, confidence interval 1.84\u201313.3). High CST<\/jats:styled-content>3 mRNA<\/jats:styled-content> levels were found in MSAp<\/jats:styled-content> caudate nuclei [expression change: 3.08 (2.98\u20133.18)] and MSAc<\/jats:styled-content> cerebella [expression change: 2.44 (2.14\u20132.88)]. I<\/jats:styled-content>n the latter there was CysC<\/jats:styled-content> over\u2010expression in P<\/jats:styled-content>urkinje cells, B<\/jats:styled-content>ergmann glia and dentate nucleus neurones. No cathepsin increase was detected in MSA<\/jats:styled-content> cerebella. High mRNA<\/jats:styled-content> levels of CST<\/jats:styled-content>3 and cathepsins B<\/jats:styled-content> and L<\/jats:styled-content>1 were observed in SCA<\/jats:styled-content>3 and CI<\/jats:styled-content> brains.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>CysC<\/jats:styled-content> changes are differentially present in the parkinsonian and cerebellar forms of MSA<\/jats:styled-content> and may play an important role in the pathogenesis of this neurodegenerative condition.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12134","type":"journal-article","created":{"date-parts":[[2014,3,10]],"date-time":"2014-03-10T05:34:37Z","timestamp":1394429677000},"page":"507-519","source":"Crossref","is-referenced-by-count":6,"title":["Cystatin C<\/scp> is differentially involved in multiple system atrophy phenotypes"],"prefix":"10.1111","volume":"41","author":[{"given":"Aintzane","family":"Urbizu","sequence":"first","affiliation":[{"name":"Servicio de Anatom\u00eda Patol\u00f3gica Instituto de Investigaci\u00f3n en Ciencias de la Salud Germans Trias i Pujol Hospital Universitario Germans Trias i Pujol Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Canet\u2010Pons","sequence":"additional","affiliation":[{"name":"Servicio de Anatom\u00eda Patol\u00f3gica Instituto de Investigaci\u00f3n en Ciencias de la Salud Germans Trias i Pujol Hospital Universitario Germans Trias i Pujol Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana M.","family":"Munoz\u2010Marmol","sequence":"additional","affiliation":[{"name":"Servicio de Anatom\u00eda Patol\u00f3gica Instituto de Investigaci\u00f3n en Ciencias de la Salud Germans Trias i Pujol Hospital Universitario Germans Trias i Pujol Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iban","family":"Aldecoa","sequence":"additional","affiliation":[{"name":"Pathology Department Hospital Cl\u00ednic Barcelona Universitat de Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria T.","family":"Lopez","sequence":"additional","affiliation":[{"name":"Servicio de Anatom\u00eda Patol\u00f3gica Instituto de Investigaci\u00f3n en Ciencias de la Salud Germans Trias i Pujol Hospital Universitario Germans Trias i Pujol Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaroslau","family":"Compta","sequence":"additional","affiliation":[{"name":"Unitat de Parkinson i Trastorns del Moviment Servicio de Neurolog\u00eda Centro de Investigaci\u00f3n en Red de Enfermedades Neurodegenerativas (CIBERNED) Hospital Cl\u00ednic\/IDIBAPS Universitat de Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramiro","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda Hospital Universitario Germans Trias i Pujol Barcelona 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