Blood-based biomarkers for Alzheimer’s disease: Assay development and clinical validation

In the past five years, major progress has been made in the field of blood-based biomarkers. This thesis shows that the key pathological hallmarks of AD, being amyloid aggregation, tau accumulation, neurodegeneration, and astrocytosis, can be reflected with biomarker measurements in blood. We found that biomarker concentrations vary across different neurodegenerative diseases and are thus valuable for differential diagnosis. We developed and validated an assay to measure the Abeta42/40 ratio in plasma, that reflected amyloid-PET positivity. Plasma P-tau181 and P-tau217 were specifically increased in participants with Alzheimer’s pathology. And NfL and GFAP contributed to biomarker panels for differential diagnosis. In addition, we developed a CSF assay that can detect acetylated tau, important for monitoring of treatment effect of tau acetylation targeting therapies. Nevertheless, there are some challenges ahead on the road to clinical implementation. The optimal panel of biomarkers for different diagnostic questions should be further established and tested in a real-world setting. Then the appropriate steps can be taken to implement blood-based biomarkers in daily clinical practice for diagnosis of AD.