Meta-Analysis of the Cystatin C(<i>CST3</i>) Gene G73A Polymorphism and Susceptibility to Alzheimer's Disease

Ye, Hua; Zhao, Hui; Lu, Xiao‐Jie; Kong, Yonggang; Jin, Huihan

doi:10.3109/00207454.2012.672502

Cited by 35 publications

(36 citation statements)

References 34 publications

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“…However, some studies have failed to show an association between CST3 and AD in a German cohort (Dodel et al, 2002), a Dutch sample with early onset AD (Roks et al, 2001), Japanese AD patients (Maruyama et al, 2001), a Finnish population (Helisalmi et al, 2009), and in early onset AD families (Parfitt et al, 1993). Other studies found a connection between the CST3 polymorphism and AD in Caucasian populations, but not in Asian populations (Hua et al, 2012), including Chinese (Wang et al, 2008). Over-all meta-analyses using this polymorphism have reported CST3 as a susceptibility gene for AD.…”

Section: Cysc and Alzheimer's Diseasementioning

confidence: 88%

Cystatin C in Alzheimer's disease

Kaur¹,

Levy²

2012

Front. Mol. Neurosci.

111

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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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Section: Cysc and Alzheimer's Diseasementioning

confidence: 88%

Cystatin C in Alzheimer's disease

Kaur¹,

Levy²

2012

Front. Mol. Neurosci.

111

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“…It is interesting to note that a polymorphism (G73A) in cystatin C has been linked to AD (43). Furthermore, cystatin C is increased in regions around A␤ deposits in the AD brain (44,45), suggesting that it may play a role in pathogenesis or in response to A␤ pathology.…”

Section: Discussionmentioning

confidence: 99%

Role of Cystatin C in Amyloid Precursor Protein-induced Proliferation of Neural Stem/Progenitor Cells

Hu¹,

Hung²,

Cui

et al. 2013

Journal of Biological Chemistry

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Background:The role of the amyloid precursor protein (APP) in neural stem/progenitor cell (NSPC) proliferation is poorly understood. Results: Immunodepletion of cystatin C from NSPC conditioned medium abrogated an effect of APP on NSPC proliferation. Conclusion: Cystatin C mediates APP-induced NSPC proliferation. Significance: The results increase understanding of mechanisms promoting NSPC survival and differentiation.

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“…6,7 Cystatin C has also been linked to risk of cognitive impairment in genetic and neuropathological studies. A common polymorphism of the cystatin C gene is associated with greater risk of Alzheimer's disease (AD), [8][9][10] and cystatin C colocalizes with bamyloid in the brain, especially in areas involved in AD pathology. 11,12 Age, sex, and muscle mass affect cystatin C, as a measure of kidney function, much less than serum creatinine.…”

Section: Objectivesmentioning

confidence: 99%

Higher Levels of Cystatin C Are Associated with Worse Cognitive Function in Older Adults with Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort Cognitive Study

Yaffe

Tamura

Ackerson

et al. 2014

J American Geriatrics Society

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OBJECTIVES Cystatin C, a measure of kidney function, has been linked to cognitive impairment, but the association between cognition and levels of cystatin C in persons with chronic kidney disease (CKD) is unknown. DESIGN/SETTING/PARTICPANTS We studied 821 participants from the Chronic Renal Insufficiency Cohort Cognitive Study with a baseline cognitive assessment completed at the same visit as serum cystatin C measurement. MEASUREMENTS Levels of serum cystatin C were categorized into tertiles; cognitive function was assessed with six neuropsychological tests. We compared scores on these tests across tertiles of cystatin C using linear regression and logistic regression to examine the association between cystatin C level and poor cognitive performance (1 SD difference from the mean). RESULTS The mean participant age was 64.9 years, 50.6% were male, and 48.6% were white. After multivariable adjustment for age, race, education, and medical comorbidities in linear models, higher levels of cystatin C were associated with worse cognition on the 3MS, Buschke Delayed Recall, Trails A, Trails B, and Boston Naming (p<0.05 for all). This association remained statistically significant for Buschke Delayed Recall (p=0.01) and Trails A (p=0.03) after additional adjustment for eGFR. Compared to the lowest tertile of cystatin C, the highest tertile was associated with increased likelihood of poor cognitive performance on Trails A (OR=2.17; 95% CI: 1.16-4.06), Trails B (OR=1.89; 95% CI: 1.09-3.27), and Boston Naming (OR=1.85; 95% CI: 1.07-3.19) after multivariate adjustment in logistic models. CONCLUSION Among patients with CKD, higher levels of serum cystatin C were associated with worse cognition and increased likelihood of poor cognitive performance on attention, executive function, and naming. Cystatin C is a marker of cognitive impairment and may be associated with cognition independent of eGFR levels.

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Meta-Analysis of the Cystatin C(CST3) Gene G73A Polymorphism and Susceptibility to Alzheimer's Disease

Abstract: The CST3 G73A polymorphism is associated with AD in Caucasian populations, but not in Asians.

Cited by 35 publications

References 34 publications

Cystatin C in Alzheimer's disease

Cystatin C in Alzheimer's disease

Role of Cystatin C in Amyloid Precursor Protein-induced Proliferation of Neural Stem/Progenitor Cells

Higher Levels of Cystatin C Are Associated with Worse Cognitive Function in Older Adults with Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort Cognitive Study

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