Understanding Molecular Biomarker Changes in Alzheimer’s Disease Using Genetically Defined Mouse Models

2020

Fluid biomarkers have become important for the monitoring of disease progression and treatment response in clinical trials. However, what is largely missing is a mechanistic understanding of what protein changes in cerebrospinal fluid and blood mean, and how they relate to processes in the brain. Our results in the first year of funding suggest that the increases of tau protein in the cerebrospinal fluid of Alzheimer´s disease subjects mainly reflect amyloid beta deposition in the brain and not (as previously thought) neurofibrillary tangle formation in the brain. We also have established that changes of neurofilament light chain protein in the blood are linked to changes in the nervous system. Finally, we have started to identify a set of proteins in cerebrospinal fluid that reflects the different stages of inflammation in the brain of Alzheimer’s patients.

2019

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.