Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the presence of extracellular amyloid plaques (senile plaques) and intracellular neurofibrillary tangles formed by hyperphosphorylated tau protein. This process leads to neuronal degradation and neuronal death. Phosphorylation of tau protein at threonine 231 (p-tau231) has been shown to be characteristic in post-mortem brain tissue of patients with AD and it can be sensitively detected in cerebrospinal fluid (CSF). Therefore, it may serve as a biomarker to support the diagnosis of AD. In this study, we analysed how well p-tau231 could differentiate between patients suffering from dementia either due or not due to AD by a sandwich enzyme immunoassay. CSF p-tau231 was significantly higher in patients with dementia due to AD than in those with dementia due to other causes. In addition, we studied different factors affecting p-tau231 levels in CSF. We found that apolipoprotein E genotype influences p-tau231 CSF levels. Gender and age did not affect p-tau231 levels in CSF. Our findings indicate that p-tau231 levels in CSF can be a valuable marker for the clinical diagnosis of AD.
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Acknowledgements
We thank Ulrike Heinze and Anke Jahn-Brodmann for the processing of biomaterial and their support with the assay performance and Prof. Dr. Oliver Wirths for performing the ApoE genotyping. Prof. Jens Wiltfang is supported by an Ilídio Pinho professorship. This study has been supported by the following grants from Instituto de Biomedicina (iBiMED) UID/BIM/04501/2013 and PTDC/DTP_PIC/5587/2014, Fundação para a Ciência e Tecnologia of the Ministério da Educação e Ciência, COMPETE program, the QREN and the European Union (Fundo Europeu de Desenvolvimento Regional).
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IL and KW are employees of AJ Roboscreen GmbH. All other authors declare no conflict of interests.
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Santos, J.R.F., Bauer, C., Schuchhardt, J. et al. Validation of a prototype tau Thr231 phosphorylation CSF ELISA as a potential biomarker for Alzheimer’s disease. J Neural Transm 126, 339–348 (2019). https://doi.org/10.1007/s00702-019-01982-5
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DOI: https://doi.org/10.1007/s00702-019-01982-5