PhD defence E.L. (Emma) van der Ende

This thesis describes the identification and validation of various biological markers (biomarkers) in blood and cerebrospinal fluid in genetic forms of frontotemporal dementia (FTD). Biomarkers could enable a more timely and accurate diagnosis of FTD, as well as inform upcoming clinical trials. The most promising biomarker is neurofilament light chain (NfL) in blood, which is elevated prior to symptom onset and remains elevated over the course of disease. Neuronal pentraxin 2 (NPTX2) is a novel biomarker which is present in decreased levels in CSF of FTD patients, probably reflecting loss of synapses in early-stage FTD. Several biomarkers of inflammation were studied, although their diagnostic value remains limited. Other novel potential biomarkers in cerebrospinal fluid were identified which require further study to assess their clinical value. Although several biomarkers for FTD have been described, the order in which they become abnormal over the course of disease was hitherto unclear. Using advanced statistical models, we estimated this sequence. These models can inform us which biomarker is the most sensitive to very early FTD, and can be used to stage patients along a disease progression continuum based on their biomarker values. Finally, the thesis provides an overview of the diverse clinical spectrum of C9orf72-associated FTD, and discusses potential explanations for the large variability in this genetic form of FTD.

The PhD defences do not take place publicly in the usual way in the Senate Hall at campus Woudestein or in the Professor Andries Querido Room at the Erasmus MC. The candidates will defend their dissertation either in a small group or online.