Abstract: A biomarker is a characteristic, which is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacologic responses to a therapeutic agent. They were increasingly used in drug development and clinical diagnostics. There were several platforms and methods used in biomarker investigation, and the mass-based methods had their contribution from the discovery stage to the qualification stage of biomarker investigation. In this review, we discussed the mass-based methods in general biomarker investigation and Alzheimer’s disease.