Characterization of the Longitudinal Trajectories of the Synaptic Blood Marker Beta-Synuclein during Alzheimer’s Disease Pathogenesis and Improvement of the Measurement Procedure

The loss of synapses in the brain is a characteristic hallmark of Alzheimer’s disease (AD) and is responsible for memory impairment. The assessment of synaptic degeneration is therefore important to detect positive effects in drug development and for early diagnosis. We recently showed that the measurement of the protein beta-synuclein could be an easily accessible blood test to track synaptic loss in the brain. However, we do not know yet the time course of beta- synuclein levels during different phases of the disease. In addition, the measurement procedure using mass spectrometry is time-consuming, and the application in clinical studies or clinical routine will benefit from a high degree of automation.

Our aim is to investigate beta-synuclein levels in blood samples from large and well-characterized clinical cohort studies that include the follow-up of patients for many years and subjects at different stages of AD. To improve the measurement procedure for beta-synuclein, we will develop an automated sample preparation protocol using the KingFisher Automated Purification system.

The analysis of beta-synuclein in the proposed project composed of 1,700 human blood samples will provide a robust basis to draft a time course of beta-synuclein changes across the different stages of AD, including the preclinical and clinical phases. It will provide us important information regarding how and at what stages we can use a blood beta-synuclein test in clinical trials or in patient care. It also will improve our knowledge about the time course of synaptic degeneration in AD, which might be an important indicator to start disease-modifying treatment strategies.