The measurements of key proteins, also known as biomarkers, in cerebrospinal fluid and blood have become important diagnostic tools for Alzheimer’s disease and other neurodegenerative disorders. However, the mechanisms behind these protein changes are poorly understood. The large heterogeneity of disease patterns among patients and possible co-morbidities are challenging obstacles to biomarker research in humans. Transgenic mouse models recapitulate pathological disease hallmarks and can help bridge the gap between biomarker findings and mechanistic readout. Moreover, novel highly sensitive technologies allow the measurement of biomarkers in very small volumes. Thus, we aim at using mouse models to find and understand novel fluid biomarkers and validate them in human samples and clinical cohorts.