Karch, André

[["dc.bibliographiccitation.firstpage","73"],["dc.bibliographiccitation.journal","Journal of Clinical Epidemiology"],["dc.bibliographiccitation.lastpage","82"],["dc.bibliographiccitation.volume","78"],["dc.contributor.author","Karch, Annika"],["dc.contributor.author","Koch, Armin"],["dc.contributor.author","Zapf, Antonia"],["dc.contributor.author","Zerr, Inga"],["dc.contributor.author","Karch, Andre"],["dc.date.accessioned","2018-11-07T10:07:22Z"],["dc.date.available","2018-11-07T10:07:22Z"],["dc.date.issued","2016"],["dc.description.abstract","Objective: To investigate how choice of gold standard biases estimates of sensitivity and specificity in studies reassessing the diagnostic accuracy of biomarkers that are already part of a lifetime composite gold standard (CGS). Study Design and Setting: We performed a simulation study based on the real-life example of the biomarker \"protein 14-3-3\" used for diagnosing Creutzfeldt Jakob disease. Three different types of gold standard were compared: perfect gold standard \"autopsy\" (available in a small fraction only; prone to partial verification bias), lifetime CGS (including the biomarker under investigation; prone to incorporation bias), and \"best available\" gold standard (autopsy if available, otherwise CGS). Results: Sensitivity was unbiased when comparing 14-3-3 with autopsy but overestimated when using CGS or \"best available\" gold standard. Specificity of 14-3-3 was underestimated in scenarios comparing 14-3-3 with autopsy (up to 24%). In contrast, overestimation (up to 20%) was observed for specificity compared with CGS; this could be reduced to 0-10% when using the \"best available\" gold standard. Conclusion: Choice of gold standard affects considerably estimates of diagnostic accuracy. Using the \"best available\" gold standard (autopsy where available, otherwise CGS) leads to valid estimates of specificity, whereas sensitivity is estimated best when tested against autopsy alone. (C) 2016 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.jclinepi.2016.03.022"],["dc.identifier.isi","000389615400010"],["dc.identifier.pmid","27107877"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39262"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","1878-5921"],["dc.relation.issn","0895-4356"],["dc.title","Partial verification bias and incorporation bias affected accuracy estimates of diagnostic studies for biomarkers that were part of an existing composite gold standard"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2189"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Molecular Neurobiology"],["dc.bibliographiccitation.lastpage","2199"],["dc.bibliographiccitation.volume","53"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Ebert, Elisabeth"],["dc.contributor.author","Stoeck, Katharina"],["dc.contributor.author","Karch, Andre"],["dc.contributor.author","Collins, Steven J."],["dc.contributor.author","Calero, Miguel"],["dc.contributor.author","Sklaviadis, Theodor"],["dc.contributor.author","Laplanche, Jean-Louis"],["dc.contributor.author","Golanska, Ewa"],["dc.contributor.author","Baldeiras, Ines"],["dc.contributor.author","Satoh, Katsuya"],["dc.contributor.author","Sanchez-Valle, Raquel"],["dc.contributor.author","Ladogana, Anna"],["dc.contributor.author","Skinningsrud, Anders"],["dc.contributor.author","Hammarin, Anna-Lena"],["dc.contributor.author","Mitrova, Eva"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Kim, Yong Sun"],["dc.contributor.author","Green, Alison"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-11-07T10:15:19Z"],["dc.date.available","2018-11-07T10:15:19Z"],["dc.date.issued","2016"],["dc.description.abstract","At present, the testing of 14-3-3 protein in cerebrospinal fluid (CSF) is a standard biomarker test in suspected sporadic Creutzfeldt-Jakob disease (sCJD) diagnosis. Increasing 14-3-3 test referrals in CJD reference laboratories in the last years have led to an urgent need to improve established 14-3-3 test methods. The main result of our study was the validation of a commercially available 14-3-3 ELISA next to the commonly used Western blot method as a high-throughput screening test. Hereby, 14-3-3 protein expression was quantitatively analyzed in CSF of 231 sCJD and 2035 control patients. We obtained excellent sensitivity/specificity values of 88 and 96 % that are comparable to the established Western blot method. Since standard protocols and preanalytical sample handling have become more important in routine diagnostic, we investigated in a further step the reproducibility and stability of 14-3-3 as a biomarker for human prion diseases. Ring trial data from 2009 to 2013 revealed an increase of Fleiss' kappa from 0.51 to 0.68 indicating an improving reliability of 14-3-3 protein detection. The stability of 14-3-3 protein under short-term and long-term storage conditions at various temperatures and after repeated freezing/thawing cycles was confirmed. Contamination of CSF samples with blood appears likely to be an important factor at a concentration of more than 2500 erythrocytes/mu L. Hemolysis of erythrocytes with significant release of 14-3-3 protein started after 2 days at room temperature. We first define clear standards for the sample handling, short- and long-term storage of CSF samples as well as the handling of blood- contaminated samples which may result in artificially elevated CSF levels of 14-3-3."],["dc.identifier.doi","10.1007/s12035-015-9167-5"],["dc.identifier.isi","000373641500011"],["dc.identifier.pmid","25947081"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40787"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Humana Press Inc"],["dc.relation.issn","1559-1182"],["dc.relation.issn","0893-7648"],["dc.title","Validation of 14-3-3 Protein as a Marker in Sporadic Creutzfeldt-Jakob Disease Diagnostic"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","71"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Dementia and Geriatric Cognitive Disorders"],["dc.bibliographiccitation.lastpage","80"],["dc.bibliographiccitation.volume","43"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Karch, Andre"],["dc.contributor.author","Golanska, Ewa"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Lange, Peter"],["dc.contributor.author","Sikorska, Beata"],["dc.contributor.author","Liberski, Pawel P."],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-11-07T10:28:45Z"],["dc.date.available","2018-11-07T10:28:45Z"],["dc.date.issued","2017"],["dc.description.abstract","Background: Several biomarkers have been proposed to discriminate sporadic Creutzfeldt-Jakob disease (sCJD) from other dementias and control cases. However, their clinical accuracy depends on the PRNP codon 129 genotype, leaving it unclear how well established markers behave in untested conditions. Methods: We analyzed 14-3-3, tau, p-tau levels, and the p-tau/ tau ratio in a population sample collected from Polish hospitals including nondementia, dementia, and definite sCJD cases and validated their parameters according to previously established cutoffs. Additionally, the correlation between biomarkers and disease duration as well as the influence of the PRNP129 polymorphism are reported. Results: The tau levels and p-tau/tau ratios differed considerably between sCJD and clinically characterized non-CJD cases (p < 0.001). p-tau was only elevated in sCJD when compared to cases without dementia (p < 0.05). Tau and the p-tau/tau ratio showed a sensitivity of 95 and 100%, respectively, in detecting sCJD cases. A negative correlation between tau levels and disease duration, but not the timing of lumbar puncture was observed. Conclusion: The present findings confirmed the value of the p-tau/tau ratio as a robust sCJD biomarker and suggest a role for tau as prognostic marker. (C) 2017 S. Karger AG, Basel."],["dc.identifier.doi","10.1159/000454802"],["dc.identifier.isi","000395664800007"],["dc.identifier.pmid","28056460"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43497"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Karger"],["dc.relation.issn","1421-9824"],["dc.relation.issn","1420-8008"],["dc.title","Cerebrospinal Fluid Biomarker-Based Diagnosis of Sporadic Creutzfeldt-Jakob Disease: A Validation Study for Previously Established Cutoffs"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Prion"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Schmidt, Christian D."],["dc.contributor.author","Karch, Andre"],["dc.contributor.author","Korth, Carsten"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-11-07T09:03:55Z"],["dc.date.available","2018-11-07T09:03:55Z"],["dc.date.issued","2012"],["dc.description.abstract","Results from recent experiments with rodents imply that Alzheimer disease might be inducible by seeding A beta peptides into recipient animals. In respect to this new experimental data, public health aspects as well as epidemiological data have to be reevaluated. In this article, the available experimental and epidemiological data are reviewed."],["dc.identifier.doi","10.4161/pri.22502"],["dc.identifier.isi","000311341100008"],["dc.identifier.pmid","23052009"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10653"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24999"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Landes Bioscience"],["dc.relation.issn","1933-6896"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","On the issue of transmissibility of Alzheimer disease A critical review"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","396"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurobiology"],["dc.bibliographiccitation.lastpage","405"],["dc.bibliographiccitation.volume","51"],["dc.contributor.author","Cramm, Maria"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Karch, Andre"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Varges, Daniel. A."],["dc.contributor.author","Mitrova, Eva"],["dc.contributor.author","Schroeder, Bjoern"],["dc.contributor.author","Raeber, Alex"],["dc.contributor.author","Kuhn, Franziska"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-11-07T10:01:38Z"],["dc.date.available","2018-11-07T10:01:38Z"],["dc.date.issued","2015"],["dc.description.abstract","The development of in vitro amplification systems allows detecting femtomolar amounts of prion protein scrapie (PrPSc) in human cerebrospinal fluid (CSF). We performed a CSF study to determine the effects of prion disease type, codon 129 genotype, PrPSc type, and other disease-related factors on the real-time quaking-induced conversion (RT-QuIC) response. We analyzed times to 10,000 relative fluorescence units, areas under the curve and the signal maximum of RT-QuIC response as seeding parameters of interest. Interestingly, type of prion disease (sporadic vs. genetic) and the PRNP mutation (E200K vs. V210I and FFI), codon 129 genotype, and PrPSc type affected RT-QuIC response. In genetic forms, type of mutation showed the strongest effect on the observed outcome variables. In sporadic CJD, MM1 patients displayed a higher RT-QuIC signal maximum compared to MV1 and VV1. Age and gender were not associated with RT-QuIC signal, but patients with a short disease course showed a higher seeding efficiency of the RT-QuIC response. This study demonstrated that PrPSc characteristics in the CSF of human prion disease patients are associated with disease subtypes and rate of decline as defined by disease duration."],["dc.identifier.doi","10.1007/s12035-014-8709-6"],["dc.identifier.isi","000349006200031"],["dc.identifier.pmid","24809690"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10255"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38062"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Humana Press Inc"],["dc.relation.issn","1559-1182"],["dc.relation.issn","0893-7648"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Characteristic CSF Prion Seeding Efficiency in Humans with Prion Diseases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","451"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Alzheimer s Disease"],["dc.bibliographiccitation.lastpage","454"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Schmidt, Christian D."],["dc.contributor.author","Karch, Andre"],["dc.contributor.author","Artjomova, Svetlana"],["dc.contributor.author","Hoeschel, Martin"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-11-07T09:30:00Z"],["dc.date.available","2018-11-07T09:30:00Z"],["dc.date.issued","2013"],["dc.description.abstract","Background: Pre-progression rates (PPR) in Alzheimer's disease (AD) have been reported to be associated with cognitive and functional decline. Objective: The objective was to reevaluate PPRs in a prospective cohort of AD patients. Methods: A prospective AD cohort was analyzed. Multiple regression was used to examine associations of PPRs with short term decline on different cognitive and functional scales (MMSE, instrumental and basic ADL, GDS, UPDRS III). Results: PPRs were only associated with first year instrumental ADL declines. Conclusion: The predictive abilities of PPRs could partially be confirmed. These findings can help to adapt patient care shortly after diagnosis."],["dc.identifier.doi","10.3233/JAD-130074"],["dc.identifier.isi","000318627800003"],["dc.identifier.pmid","23435410"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31196"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Ios Press"],["dc.relation.issn","1387-2877"],["dc.title","Pre-Progression Rates in Alzheimer's Disease Revisited"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1896"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Molecular Neurobiology"],["dc.bibliographiccitation.lastpage","1904"],["dc.bibliographiccitation.volume","53"],["dc.contributor.author","Cramm, Maria"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Karch, Andre"],["dc.contributor.author","Mitrova, Eva"],["dc.contributor.author","Kuhn, Franziska"],["dc.contributor.author","Schroeder, Bjoern"],["dc.contributor.author","Raeber, Alex"],["dc.contributor.author","Varges, Daniel. A."],["dc.contributor.author","Kim, Yong-Sun"],["dc.contributor.author","Satoh, Katsuya"],["dc.contributor.author","Collins, Steven J."],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-11-07T10:16:36Z"],["dc.date.available","2018-11-07T10:16:36Z"],["dc.date.issued","2016"],["dc.description.abstract","Real-time quaking-induced conversion (RT-QuIC) allows the amplification of miniscule amounts of scrapie prion protein (PrPSc). Recent studies applied the RT-QuIC methodology to cerebrospinal fluid (CSF) for diagnosing human prion diseases. However, to date, there has not been a formal multi-centre assessment of the reproducibility, validity and stability of RT-QuIC in this context, an indispensable step for establishment as a diagnostic test in clinical practice. In the present study, we analysed CSF from 110 prion disease patients and 400 control patients using the RT-QuIC method under various conditions. In addition, \"blinded\" ring trials between different participating sites were performed to estimate reproducibility. Using the previously established cut-off of 10,000 relative fluorescence units (rfu), we obtained a sensitivity of 85 % and a specificity of 99 %. The multi-centre inter-laboratory reproducibility of RT-QuIC revealed a Fleiss' kappa value of 0.83 (95 % CI: 0.40-1.00) indicating an almost perfect agreement. Moreover, we investigated the impact of short-term CSF storage at different temperatures, long-term storage, repeated freezing and thawing cycles and the contamination of CSF with blood on the RT-QuIC seeding response. Our data indicated that the PrPSc seed in CSF is stable to any type of storage condition but sensitive to contaminations with blood (> 1250 erythrocytes/mu L), which results in a false negative RT-QuIC response. Fresh blood-contaminated samples (3 days) can be rescued by removal of erythrocytes. The present study underlines the reproducibility and high stability of RT-QuIC across various CSF storage conditions with a remarkable sensitivity and specificity, suggesting RT-QuIC as an innovative and robust diagnostic method."],["dc.identifier.doi","10.1007/s12035-015-9133-2"],["dc.identifier.isi","000372263600045"],["dc.identifier.pmid","25823511"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11732"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41064"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Humana Press Inc"],["dc.relation.issn","1559-1182"],["dc.relation.issn","0893-7648"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Stability and Reproducibility Underscore Utility of RT-QuIC for Diagnosis of Creutzfeldt-Jakob Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3051"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","3061"],["dc.bibliographiccitation.volume","135"],["dc.contributor.author","Stoeck, Katharina"],["dc.contributor.author","Sanchez-Juan, Pascual"],["dc.contributor.author","Gawinecka, Joanna"],["dc.contributor.author","Green, Alison"],["dc.contributor.author","Ladogana, Anna"],["dc.contributor.author","Pocchiari, Maurizio"],["dc.contributor.author","Sanchez-Valle, Raquel"],["dc.contributor.author","Mitrova, Eva"],["dc.contributor.author","Sklaviadis, Theodor"],["dc.contributor.author","Kulczycki, Jerzy"],["dc.contributor.author","Slivarichova, Dana"],["dc.contributor.author","Saiz, Albert"],["dc.contributor.author","Calero, Miguel"],["dc.contributor.author","Knight, Richard"],["dc.contributor.author","Aguzzi, Adriano"],["dc.contributor.author","Laplanche, Jean-Louis"],["dc.contributor.author","Peoc'h, Katell"],["dc.contributor.author","Schelzke, Gabi"],["dc.contributor.author","Karch, Andre"],["dc.contributor.author","van Duijn, Cornelia M."],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-11-07T09:04:59Z"],["dc.date.available","2018-11-07T09:04:59Z"],["dc.date.issued","2012"],["dc.description.abstract","To date, cerebrospinal fluid analysis, particularly protein 14-3-3 testing, presents an important approach in the identification of Creutzfeldt-Jakob disease cases. However, one special point of criticism of 14-3-3 testing is the specificity in the differential diagnosis of rapid dementia. The constant observation of increased cerebrospinal fluid referrals in the national surveillance centres over the last years raises the concern of declining specificity due to higher number of cerebrospinal fluid tests performed in various neurological conditions. Within the framework of a European Community supported longitudinal multicentre study ('cerebrospinal fluid markers') we analysed the spectrum of rapid progressive dementia diagnoses, their potential influence on 14-3-3 specificity as well as results of other dementia markers (tau, phosphorylated tau and amyloid-beta(1-42)) and evaluated the specificity of 14-3-3 in Creutzfeldt-Jakob disease diagnosis for the years 1998-2008. A total of 29 022 cerebrospinal fluid samples were analysed for 14-3-3 protein and other cerebrospinal fluid dementia markers in patients with rapid dementia and suspected Creutzfeldt-Jakob disease in the participating centres. In 10 731 patients a definite diagnosis could be obtained. Protein 14-3-3 specificity was analysed for Creutzfeldt-Jakob disease with respect to increasing cerebrospinal fluid tests per year and spectrum of differential diagnosis. Ring trials were performed to ensure the comparability between centres during the reported time period. Protein 14-3-3 test specificity remained high and stable in the diagnosis of Creutzfeldt-Jakob disease during the observed time period across centres (total specificity 92%; when compared with patients with definite diagnoses only: specificity 90%). However, test specificity varied with respect to differential diagnosis. A high 14-3-3 specificity was obtained in differentiation to other neurodegenerative diseases (95-97%) and non-neurological conditions (91-97%). We observed lower specificity in the differential diagnoses of acute neurological diseases (82-87%). A marked and constant increase in cerebrospinal fluid test referrals per year in all centres did not influence 14-3-3 test specificity and no change in spectrum of differential diagnosis was observed. Cerebrospinal fluid protein 14-3-3 detection remains an important test in the diagnosis of Creutzfeldt-Jakob disease. Due to a loss in specificity in acute neurological events, the interpretation of positive 14-3-3 results needs to be performed in the clinical context. The spectrum of differential diagnosis of rapid progressive dementia varied from neurodegenerative dementias to dementia due to acute neurological conditions such as inflammatory diseases and non-neurological origin."],["dc.description.sponsorship","European Commission [QLG3-CT-2002-81606, 222887, 01ED1201A]"],["dc.identifier.doi","10.1093/brain/aws238"],["dc.identifier.isi","000310156700015"],["dc.identifier.pmid","23012332"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8382"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25223"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0006-8950"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Cerebrospinal fluid biomarker supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias: a longitudinal multicentre study over 10 years"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","371"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The American Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","382"],["dc.bibliographiccitation.volume","95"],["dc.contributor.author","Minikel, Eric Vallabh"],["dc.contributor.author","Zerr, Inga"],["dc.contributor.author","Collins, Steven J."],["dc.contributor.author","Ponto, Claudia"],["dc.contributor.author","Boyd, Alison"],["dc.contributor.author","Klug, Genevieve M. J. A."],["dc.contributor.author","Karch, Andre"],["dc.contributor.author","Kenny, Joanna"],["dc.contributor.author","Collinge, John"],["dc.contributor.author","Takada, Leonel T."],["dc.contributor.author","Forner, Sven"],["dc.contributor.author","Fong, Jamie C."],["dc.contributor.author","Mead, Simon"],["dc.contributor.author","Geschwind, Michael D."],["dc.date.accessioned","2018-11-07T09:33:47Z"],["dc.date.available","2018-11-07T09:33:47Z"],["dc.date.issued","2014"],["dc.description.abstract","Anticipation is the phenomenon whereby age of onset in genetic disease decreases in successive generations. Three independent reports have claimed anticipation in Creutzfeldt-Jakob disease (CJD) caused by the c.598G>A mutation in PRNP encoding a p.Glu200Lys (E200K) substitution in the prion protein. If confirmed, this finding would carry clear implications for genetic counseling. We analyzed pedigrees with this mutation from four prion centers worldwide (n = 217 individuals with the mutation) to analyze age of onset and death in affected and censored individuals. We show through simulation that selective ascertainment of individuals whose onset falls within the historical window since the mutation's 1989 discovery is sufficient to create robust false signals both of anticipation and of heritability of age of onset. In our data set, the number of years of anticipation observed depends upon how strictly the data are limited by the ascertainment window. Among individuals whose disease was directly observed at a study center, a 28-year difference between parent and child age of onset is observed (p = 0.002), but including individuals ascertained retrospectively through family history reduces this figure to 7 years (p = 0.005). Applying survival analysis to the most thoroughly ascertained subset of data eliminates the signal of anticipation. Moreover, even non-CJD deaths exhibit 16 years anticipation (p = 0.002), indicating that ascertainment bias can entirely explain observed anticipation. We suggest that reports of anticipation in genetic prion disease are driven entirely by ascertainment bias. Guidelines for future studies claiming statistical evidence for anticipation are suggested."],["dc.identifier.doi","10.1016/j.ajhg.2014.09.003"],["dc.identifier.isi","000342654300003"],["dc.identifier.pmid","25279981"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32045"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cell Press"],["dc.relation.issn","1537-6605"],["dc.relation.issn","0002-9297"],["dc.title","Ascertainment Bias Causes False Signal of Anticipation in Genetic Prion Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","577"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Alzheimer s & Dementia"],["dc.bibliographiccitation.lastpage","589"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Karch, Andre"],["dc.contributor.author","Cramm, Maria"],["dc.contributor.author","Lange, Peter"],["dc.contributor.author","Gherib, Kerim"],["dc.contributor.author","Varges, Daniel. A."],["dc.contributor.author","Schmidt, Christian D."],["dc.contributor.author","Zerr, Inga"],["dc.contributor.author","Stoeck, Katharina"],["dc.date.accessioned","2018-11-07T10:14:52Z"],["dc.date.available","2018-11-07T10:14:52Z"],["dc.date.issued","2016"],["dc.description.abstract","Introduction: The analysis of cerebrospinal fluid biomarkers gains importance in clinical routine and is effective in substantiating dementia diagnosis in the differential diagnostic context. Methods: We evaluated the levels of beta-amyloid (A beta) 42, A beta 40, tau, and P-tau in a large patient population subdivided into prion diseases, tauopathies, synucleinopathies, and controls. Diagnostic test evaluation was assessed by ROC area under the curve analysis. Results: High tau levels were detected in sporadic Creutzfeldt-Jakob disease (sCJD) and high P-tau levels in Alzheimer's disease (AD) and sCJD. A beta 40 was lower exclusively in prionopathies, but low A beta 42 was detected in AD, sCJD, and Lewy body dementia. When disease groups were stratified according to the underlying proteinopathy, we detected disease-type specificities for all biomarkers. P-tau/tau, A beta 42/40, A beta 42/tau, and A beta 40/tau ratios proved valuable in discriminating disease groups and controls, especially P-tau/tau ratio in the identification of sCJD cases. Discussion: Combining the biomarker panel allows differentiating between various types of neuro-degenerative dementias and contributes to a better understanding of their pathophysiological processes. (C) 2015 Alzheimer's Association. Published by Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.jalz.2015.10.009"],["dc.identifier.isi","000376054200007"],["dc.identifier.pmid","26718584"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40704"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","1552-5279"],["dc.relation.issn","1552-5260"],["dc.title","Comparative analysis of cerebrospinal fluid biomarkers in the differential diagnosis of neurodegenerative dementia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]