Abstract Body

There is need for biomarkers that improve the diagnostic work-up of neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson's disease (PD), which can be used in both clinical practice and trials. In this talk I will focus on recent advances in fluid and PET imaging biomarkers for tau pathology in AD. We have shown that a neocortical tau-PET signal in cognitively unimpaired individuals is associated with a very high risk of developing cognitive impairment in the next few years, supporting the notion of “preclinical AD”. We have recently also shown that mass spectrometry-based measures of p-tau217/tau217 is superior to all currently available immunoassays for detection of plasma p-tau, and it is not significantly affected by comorbidities like chronic kidney disease. Further, certain fluid tau variants like MTBR-tau243 and p-tau205 are more closely linked to tau tangle pathology and change later in the disease compared to p-tau231, p-tau217 and p-tau181. Next, I will discuss what steps are needed for clinical implementation of these new fluid tau biomarkers. There will also be a discussion on how blood and PET biomarkers can improve clinical trials evaluating disease modifying therapies, when it comes to enrichment of study participants to be included in the trials as well as when measuring relevant effects of the treatments. Finally, I will discuss the potential use of novel seeding aggregation assays for a-synuclein pathology for early detection of Lewy body disease in the context of selecting appropriate participants for clinical trials.