Quantification of cystatin C in cerebrospinal fluid from various neurological disorders and correlation with G73A polymorphism in CST3

Yamamoto-Watanabe, Yukiko; Watanabe, Mitsunori; Jackson, Mandy; Akimoto, Hiroyuki; Sugimoto, Kazuhiro; Yasujima, Minoru; Wakasaya, Yasuhito; Matsubara, Etsuro; Kawarabayashi, Tatsuhiko; Harigaya, Yasuo; Lyndon, Alastair Robert; Shoji, Mikio

doi:10.1016/j.brainres.2010.09.033

Cited by 25 publications

(18 citation statements)

References 32 publications

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“…Decreased CSF CysC in patients with characteristic amyloid deposits may be related to its deposition occurring secondarily to Αβ deposition [13] in the brain. Several studies documented an association of the BB genotype of the CysC-encoding gene CST3 with decreased plasma [24] and CSF [35], [37] CysC levels, and this association may be due to a less efficient cleavage of the signal peptide, resulting in a reduced secretion of CysC [38]. These results, in combination with our data, suggest that decreased levels of CSF CysC in dementia patients with characteristic amyloid deposits may be explained by abnormal deposition in amyloid plaques in the brain, reduced secretion of the protein or both.…”

Section: Discussionmentioning

confidence: 99%

Alterations of CSF Cystatin C Levels and Their Correlations with CSF Αβ40 and Αβ42 Levels in Patients with Alzheimer's Disease, Dementia with Lewy Bodies and the Atrophic Form of General Paresis

et al. 2013

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Immunohistochemical studies have revealed that cystatin C (CysC) co-localizes with amyloid-β (Αβ) in amyloid-laden vascular walls and in the senile plaque cores of amyloid. In vitro and in vivo animal studies suggest that CysC protects against neurodegeneration by inhibition of cysteine proteases, inhibition of Αβ aggregation, induction of autophagy and induction of cell division. CysC levels may be altered and may have a potential link with cerebrospinal fluid (CSF) Aβ levels in various types of dementia with characteristic amyloid deposits, such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and the atrophic form of general paresis (AF-GP). We assessed the serum and CSF levels of CysC and the CSF levels of Aβ40 and Aβ42 in patients with AD (n = 51), DLB (n = 26) and AF-GP (n = 43) and normal controls (n = 30). Using these samples, we explored the correlation between CSF CysC and CSF Aβ levels. We found that in comparison to the normal control group, both CSF CysC and CSF Aβ42 levels were significantly lower in all three dementia groups (all p<0.001); serum CysC levels were the same in the AD and DLB groups, and were lower in the AF-GP group (p = 0.008). The CSF CysC levels were positively correlated with both the CSF Aβ40 and Aβ42 levels in the AD, AF-GP and normal control groups (r = 0.306∼0.657, all p<0.05). Lower CSF CysC levels might be a common feature in dementia with characteristic amyloid deposits. Our results provide evidence for the potential role of CysC involvement in Aβ metabolism and suggest that modulation of the CysC level in the brain might produce a disease-modifying effect in dementia with characteristic amyloid deposits.

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Section: Discussionmentioning

confidence: 99%

Alterations of CSF Cystatin C Levels and Their Correlations with CSF Αβ40 and Αβ42 Levels in Patients with Alzheimer's Disease, Dementia with Lewy Bodies and the Atrophic Form of General Paresis

et al. 2013

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“…CSF levels of clusterin have been reported to be increased (Přikrylová Vranová et al, 2010; Vranová et al, 2014) or normal (van Dijk et al, 2013a), tissue transglutaminase (Vermes et al, 2004) increased in PD, and cystatin C normal in PD (Přikrylová Vranová et al, 2010; Yamamoto-Watanabe et al, 2010) and decreased in MSA (Yamamoto-Watanabe et al, 2010). …”

Section: Proteins Involved In the Pathogenesis Of Parkinson's Diseasementioning

confidence: 99%

Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease

Jiménez‐Jiménez¹,

Alonso‐Navarro

García‐Martín

et al. 2014

Front. Cell. Neurosci.

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The blood-brain barrier supplies brain tissues with nutrients and filters certain compounds from the brain back to the bloodstream. In several neurodegenerative diseases, including Parkinson's disease (PD), there are disruptions of the blood-brain barrier. Cerebrospinal fluid (CSF) has been widely investigated in PD and in other parkinsonian syndromes with the aim of establishing useful biomarkers for an accurate differential diagnosis among these syndromes. This review article summarizes the studies reported on CSF levels of many potential biomarkers of PD. The most consistent findings are: (a) the possible role of CSF urate on the progression of the disease; (b) the possible relations of CSF total tau and phosphotau protein with the progression of PD and with the preservation of cognitive function in PD patients; (c) the possible value of CSF beta-amyloid 1-42 as a useful marker of further cognitive decline in PD patients, and (d) the potential usefulness of CSF neurofilament (NFL) protein levels in the differential diagnosis between PD and other parkinsonian syndromes. Future multicentric, longitudinal, prospective studies with long-term follow-up and neuropathological confirmation would be useful in establishing appropriate biomarkers for PD.

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“…The CST3 gene G73A polymorphism functionally affects CysC plasma levels (Noto et al, 2005) and CysC CSF levels (Maetzler et al, 2010; Yamamoto-Watanabe et al, 2010). Maetzler and colleagues (Maetzler et al, 2010) showed that the BB genotype of the CST3 gene is associated with reduced CSF CysC levels in patients with Lewy body disease with dementia.…”

Section: Cysc and Alzheimer's Diseasementioning

confidence: 99%

Cystatin C in Alzheimer's disease

Kaur¹,

Levy²

2012

Front. Mol. Neurosci.

110

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Changes in expression and secretion levels of cystatin C (CysC) in the brain in various neurological disorders and in animal models of neurodegeneration underscore a role for CysC in these conditions. A polymorphism in the CysC gene (CST3) is linked to increased risk for Alzheimer's disease (AD). AD pathology is characterized by deposition of oligomeric and fibrillar forms of amyloid β (Aβ) in the neuropil and cerebral vessel walls, neurofibrillary tangles composed mainly of hyperphosphorylated tau, and neurodegeneration. The implication of CysC in AD was initially suggested by its co-localization with Aβ in amyloid-laden vascular walls, and in senile plaque cores of amyloid in the brains of patients with AD, Down's syndrome, hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D), and cerebral infarction. CysC also co-localizes with Aβ amyloid deposits in the brains of non-demented aged individuals. Multiple lines of research show that CysC plays protective roles in AD. In vitro studies have shown that CysC binds Aβ and inhibits Aβ oligomerization and fibril formation. In vivo results from the brains and plasma of Aβ-depositing transgenic mice confirmed the association of CysC with the soluble, non-pathological form of Aβ and the inhibition of Aβ plaques formation. The association of CysC with Aβ was also found in brain and in cerebrospinal fluid (CSF) from AD patients and non-demented control individuals. Moreover, in vitro results showed that CysC protects neuronal cells from a variety of insults that may cause cell death, including cell death induced by oligomeric and fibrillar Aβ. These data suggest that the reduced levels of CysC manifested in AD contribute to increased neuronal vulnerability and impaired neuronal ability to prevent neurodegeneration. This review elaborates on the neuroprotective roles of CysC in AD and the clinical relevance of this protein as a therapeutic agent.

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Quantification of cystatin C in cerebrospinal fluid from various neurological disorders and correlation with G73A polymorphism in CST3

Cited by 25 publications

References 32 publications

Alterations of CSF Cystatin C Levels and Their Correlations with CSF Αβ40 and Αβ42 Levels in Patients with Alzheimer's Disease, Dementia with Lewy Bodies and the Atrophic Form of General Paresis

Alterations of CSF Cystatin C Levels and Their Correlations with CSF Αβ40 and Αβ42 Levels in Patients with Alzheimer's Disease, Dementia with Lewy Bodies and the Atrophic Form of General Paresis

Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease

Cystatin C in Alzheimer's disease

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