Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Linda van Waalwijk van Doorn (Donders series 444)

27 August 2020

Promotors: prof. dr. C. Klijn, dr. ir. M. Verbeek
Co-promotor: dr. H. Kuiperij

Cerebrospinal fluid biomarker assays for Alzheimer's disease: standardization, validation and analysis of confounders

In the search of improvement of diagnostic tools in patients suffering from AD, this thesis seeks to contribute to the clinical application of newly developed and established biomarkers. The emphasis will be on the validation process, that is necessary to establish globally accepted reliable clinical biomarker tests for the diagnostic assessment and support of new treatment modalities. Aspects to be encountered are standardization of methodology, technical reproducibility, calibration procedures, test-retest variability, inter-rater variability, validation process of performance parameters and possible confounding factors. We aim to improve the reliability and reproducibility of CSF biomarker measurements that may support daily practice clinical assessment of AD by (1) standardization and technical validation of biomarker assays, (2) studying effects of biological confounding factors on the performance of such assays. In this thesis we underline the relevance of standardization and validation of CSF biomarker quantification methods and the effect of possible biological confounding factors. Our results increase the knowledge about technical and biological confounders that may be relevant for CSF biomarker quantification and interpretation. This knowledge can be applied for standardized development and implementation of novel CSF biomarker assays.