O2–09–03: Detection and quantification of novel tau/phospho‐tau epitopes in CSF using a multiplex assay approachстатья из журнала
Аннотация: Tau and phospho-tau (p-tau) isoforms in cerebrospinal fluid (CSF) are considered as diagnostic markers for staging the progression of Alzheimer's disease (AD) or for differentiating AD from other dementia forms. So far, only four (pS199, pT181, pT231, pS396–404) of the more than 40 abnormally phosphorylated sites in protein tau have been examined as potential biomarker. To the best of our knowledge only one multicenter study has compared different p-tau assays in a clinical setting. The possible clinical value of the p-tau sites for differential dementia diagnosis requires larger studies and the availability of novel tools for their quantification. Multiplex-assays were developed to study different tau isoforms in CSF simultaneously, based on xMAP ™ -technology (Luminex). Combining the different tau-epitopes in a single peptide sequence allows calibration of two (or more) analytes concurrently, such as pS198-tau or oligomeric tau. One of the novel p-tau sites detected with the assays is pS198, which is abnormally phosphorylated in Paired Helical Filaments (PHFs) in AD but not in PHFs isolated from brains of patients with Progressive Supranuclear Palsy (PSP). By using the same antibody as capture and detector antibody, we are able to quantify tau-oligomers as well. The qualification of the multiplex-assays is based on phosphorylated and aggregated protein tau isolated and characterized from yeast strains expressing such modified tau. The analytical characteristics of the multi-tau assays are similar to ELISA with respect to standard curve accuracy, precision, robustness and parallelism, but superior with respect to analytical sensitivity. Current CSF-studies with the assays confirm the increase of CSF-tau in AD versus controls, but more elaborate studies of clinical diagnostic groups, such as FTD, PSP and/or VAD will be presented. The assay format for multi-tau/p-tau detection and quantification will allow for a more efficient selection of the most relevant tau species in a clinical-diagnostic setting and might be used to monitor tau-mediated disease-modifying therapies.
Год издания: 2013
Авторы: Ann De Vos, Dirk Jacobs, Eugeen Vanmechelen, Joris Winderickx, Jeff Van den Brande, Sebastiaan Engelborghs, Hanne Struyfs, Kaj Blennow, Henrik Zetterberg
Издательство: Wiley
Источник: Alzheimer s & Dementia
Ключевые слова: Alzheimer's disease research and treatments, Advanced Proteomics Techniques and Applications, Metabolomics and Mass Spectrometry Studies
Открытый доступ: bronze
Том: 9
Выпуск: 4S_Part_8