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Cystatin C is differentially involved in multiple system atrophy phenotypes
Author(s) -
Urbizu Aintzane,
CanetPons Julia,
MunozMarmol Ana M.,
Aldecoa Iban,
Lopez Maria T.,
Compta Yaroslau,
Alvarez Ramiro,
Ispierto Lourdes,
Tolosa Eduardo,
Ariza Aurelio,
Beyer Katrin
Publication year - 2015
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12134
Subject(s) - cystatin c , atrophy , cathepsin , cathepsin b , neurodegeneration , immunohistochemistry , cerebellum , pathology , phenotype , biology , cystatin , microbiology and biotechnology , medicine , endocrinology , gene , genetics , biochemistry , disease , renal function , enzyme
Aims As cystatin C ( CysC ) is involved in some forms of neurodegeneration, we investigated the possible relationship between CysC and multiple system atrophy ( MSA ), including its parkinsonian ( MSAp ) and cerebellar ( MSAc ) phenotypes. Methods Cystatin C gene ( CST 3) haplotypes were determined by PCR followed by KspI digestion in 50 MSA patients and 108 controls. CST 3 and cathepsins B , D and L 1 mRNA levels were studied in frozen post‐mortem caudate nucleus and cerebellar samples of eight MSAp , four MSAc and 18 control brains and analysed by the ΔΔ C t method. CysC immunohistochemistry was performed on three MSAp , three MSAc and three control cerebella. Additionally, determination of CST 3 and cathepsins B , D and L 1 mRNA levels and immunohistochemistry for CysC were carried out in cerebella from three patients with paraneoplastic cerebellar degeneration, three with spinocerebellar ataxia (type 3, SCA 3) and three with cerebellar ischaemia ( CI ). Results In the set of blood samples, the CST 3 B ‐haplotype was associated with MSAp ( OR 4.86, confidence interval 1.84–13.3). High CST 3 mRNA levels were found in MSAp caudate nuclei [expression change: 3.08 (2.98–3.18)] and MSAc cerebella [expression change: 2.44 (2.14–2.88)]. I n the latter there was CysC over‐expression in P urkinje cells, B ergmann glia and dentate nucleus neurones. No cathepsin increase was detected in MSA cerebella. High mRNA levels of CST 3 and cathepsins B and L 1 were observed in SCA 3 and CI brains. Conclusions CysC changes are differentially present in the parkinsonian and cerebellar forms of MSA and may play an important role in the pathogenesis of this neurodegenerative condition.