Serum and cerebrospinal fluid cystatin C levels in vascular and Alzheimer's dementia

Kálmán, János; Márki-Zay, János; Juhász, Anna; Sántha, A; Dux, L.; Janka, Zoltán

doi:10.1034/j.1600-0404.2000.101004279.x

Cited by 22 publications

(7 citation statements)

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“…We found that plasma and CSF levels of cystatin C did not discriminate between AD patients and age and gender-matched control patients, in agreement with previous findings [30]. Also, CSF measurements of cystatin C by sandwich ELISA in large collectives of sCJD, vCJD, and control samples was not discriminatory between these three groups.…”

Section: Discussionsupporting

confidence: 90%

Urinary α1-Antichymotrypsin: A Biomarker of Prion Infection

Miele¹,

Seeger²,

Marino³

et al. 2008

PLoS ONE

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The occurrence of blood-borne prion transmission incidents calls for identification of potential prion carriers. However, current methods for intravital diagnosis of prion disease rely on invasive tissue biopsies and are unsuitable for large-scale screening. Sensitive biomarkers may help meeting this need. Here we scanned the genome for transcripts elevated upon prion infection and encoding secreted proteins. We found that α1-antichymotrypsin (α1-ACT) was highly upregulated in brains of scrapie-infected mice. Furthermore, α1-ACT levels were dramatically increased in urine of patients suffering from sporadic Creutzfeldt-Jakob disease, and increased progressively throughout the disease. Increased α1-ACT excretion was also found in cases of natural prion disease of animals. Therefore measurement of urinary α1-ACT levels may be useful for monitoring the efficacy of therapeutic regimens for prion disease, and possibly also for deferring blood and organ donors that may be at risk of transmitting prion infections.

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Section: Discussionsupporting

confidence: 90%

Urinary α1-Antichymotrypsin: A Biomarker of Prion Infection

Miele¹,

Seeger²,

Marino³

et al. 2008

PLoS ONE

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“…DISCUSSION In this study, lower serum levels of cystatin C were associated with higher incidence of AD. Previous studies of the association between serum cystatin C and AD have reported conflicting results, one reporting no difference in cystatin C levels between AD cases and controls, 24 one reporting high cystatin C levels in AD, 25 and a third reporting low levels of cystatin C in AD. 12 These studies may all be limited by a crosssectional case-control design and limited adjustments for potential confounders.…”

Section: Resultsmentioning

confidence: 77%

“…12 These studies may all be limited by a crosssectional case-control design and limited adjustments for potential confounders. Also, the two first studies had smaller study samples (n ϭ 41 and n ϭ 66) 24,25 compared with the third (n ϭ 646). and that staining with cystatin C is increased in AD brains, whereas it is absent or minimal in brains from individuals who remained cognitively intact during life.…”

Section: Resultsmentioning

confidence: 99%

Serum cystatin C and the risk of Alzheimer disease in elderly men

Sundelöf

Ärnlöv²,

Ingelsson³

et al. 2008

Neurology

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“…The levels of at least 7 of the novel biomarkers have been evaluated in AD subjects in other studies: no change was observed in plasma PAI-1 levels [44]; in agreement with our findings, two studies have reported increased CSF MIF in AD and MCI subjects [45], [46]; also consistent with our findings, increased fibrinogen levels have been observed in AD and MCI CSF [47] and in AD plasma [48], and increased plasma levels have been associated with an increased risk of future dementia [49]; results have been mixed regarding CSF FAS levels in AD [50], [51]; AD plasma/serum VEGF levels have been reported to be unchanged [52], [53], decreased [54], and increased [55], while CSF levels have been reported to be unchanged [56] or increased [57]; no change in CSF or serum levels of TNF RII in AD has been reported [58]; cystatin C findings have been inconsistent, with reports of serum/plasma levels unchanged [59], increased in AD [60] or in those who later develop AD [61], and decreased [62] or decreased levels associated with increased risk of future AD [63], while CSF levels have been reported to be unchanged [59], [64], decreased [65], or increased [21]. These inconsistent results may be due in part to the existence of a truncated form of cystatin C, which was found to be increased in AD CSF, while the full length protein was decreased [20], [21].…”

Section: Discussionmentioning

confidence: 99%

Multiplexed Immunoassay Panel Identifies Novel CSF Biomarkers for Alzheimer's Disease Diagnosis and Prognosis

et al. 2011

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BackgroundClinicopathological studies suggest that Alzheimer's disease (AD) pathology begins ∼10–15 years before the resulting cognitive impairment draws medical attention. Biomarkers that can detect AD pathology in its early stages and predict dementia onset would, therefore, be invaluable for patient care and efficient clinical trial design. We utilized a targeted proteomics approach to discover novel cerebrospinal fluid (CSF) biomarkers that can augment the diagnostic and prognostic accuracy of current leading CSF biomarkers (Aβ42, tau, p-tau181).Methods and FindingsUsing a multiplexed Luminex platform, 190 analytes were measured in 333 CSF samples from cognitively normal (Clinical Dementia Rating [CDR] 0), very mildly demented (CDR 0.5), and mildly demented (CDR 1) individuals. Mean levels of 37 analytes (12 after Bonferroni correction) were found to differ between CDR 0 and CDR>0 groups. Receiver-operating characteristic curve analyses revealed that small combinations of a subset of these markers (cystatin C, VEGF, TRAIL-R3, PAI-1, PP, NT-proBNP, MMP-10, MIF, GRO-α, fibrinogen, FAS, eotaxin-3) enhanced the ability of the best-performing established CSF biomarker, the tau/Aβ42 ratio, to discriminate CDR>0 from CDR 0 individuals. Multiple machine learning algorithms likewise showed that the novel biomarker panels improved the diagnostic performance of the current leading biomarkers. Importantly, most of the markers that best discriminated CDR 0 from CDR>0 individuals in the more targeted ROC analyses were also identified as top predictors in the machine learning models, reconfirming their potential as biomarkers for early-stage AD. Cox proportional hazards models demonstrated that an optimal panel of markers for predicting risk of developing cognitive impairment (CDR 0 to CDR>0 conversion) consisted of calbindin, Aβ42, and age.Conclusions/SignificanceUsing a targeted proteomic screen, we identified novel candidate biomarkers that complement the best current CSF biomarkers for distinguishing very mildly/mildly demented from cognitively normal individuals. Additionally, we identified a novel biomarker (calbindin) with significant prognostic potential.

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Serum and cerebrospinal fluid cystatin C levels in vascular and Alzheimer's dementia

Abstract: These results indicate that lower than normal CSF cystatin C level is not a diagnostic marker in ischemic VD and CAA related to AD.

Cited by 22 publications

References 0 publications

Urinary α1-Antichymotrypsin: A Biomarker of Prion Infection

Urinary α1-Antichymotrypsin: A Biomarker of Prion Infection

Serum cystatin C and the risk of Alzheimer disease in elderly men

Multiplexed Immunoassay Panel Identifies Novel CSF Biomarkers for Alzheimer's Disease Diagnosis and Prognosis

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