blood-based makers for neurodegeneration in early stages of Alzheimer’s disease

This project proposal is an important study that evaluates biomarker changes in a way that is complementary ‐ but not equal ‐ to the biomarker project in another studyy(FWO aspirant study by Steffie De Meyer). In particular, this project aims at evaluating how biomarkers of neurodegeneration including NfL and synaptic markers change in the period (ten years) before AD patients start to have cognitive complaints. For this purpose, we have a unique cohort of 204 patients that have developed clinical sporadic Alzheimer’s disease (sAD) for whom well‐stored presymptomatic serum samples i.e. sampled within the decade preceding the onset of clinical symptoms are available. Indeed, the clinical laboratory of the University Hospitals Leuven (UZ Leuven) (with dr. Poesen as a clinical pathologist) systematically performs long-term storage (at ‐20°C) of serum samples in case serological tests are ordered. We retrospectively retrieved samples from 204 patients, all collected in a period of ten years before the presumed symptom onset (i.e. two years before diagnosis), further termed presymptomatic samples. Of note, this sampling occurred during routine clinical visits for other reasons than cognitive complaints between 2006 and 2019. This cohort will now allow us to investigate if blood‐based AD biomarkers change prior to symptom onset in sAD. Moreover, it will now provide insights into how these changes relate to time to clinical AD onset. In our FWO project, we evaluate hyperphosphorylated tau (pTau) and glial fibrillary acidic protein (GFAP) blood biomarkers. Now, we want to study NfL and synaptic markers in the presymptomatic phase, more specifically within the ten years prior to overt cognitive symptoms in AD. The overall project will compare the changes in pTau and GFAP to the changes in NfL of in those of synaptic markers in the stage before the complaints of AD become overt