Background
Current biomarkers for Alzheimer’s Disease (AD) are lacking in their ability to discriminate between AD and non-AD dementias, as well as to characterize the multifactorial nature of AD pathology. An article from Professor Charlotte Teunissen’s group in Amsterdam provides a striking example of how large-scale biomarker discovery can be used to identify and validate informative protein signatures using one scalable technology. In a study of individuals with different stages of AD, non-AD dementia and healthy controls, they characterized the cerebrospinal fluid (CSF) proteomes of these individuals using 11 Olink® Target 96 panels
Outcome
The discovery phase identified over 100 proteins dysregulated in AD compared to the other two groups. Data-driven modeling then identified a 8-protein signature that discriminated AD vs controls with an AUC of 0.96, as well as a 9-protein signature that discriminated AD vs non-AD dementia with an AUC of 0.87. After verifying these signatures in additional cohorts, 12 proteins were used to construct a custom biomarker panel that showed high performance in a validation study, with an AUC of 0.95 for AD vs controls and 0.79 for AD vs non-AD dementia. This custom panel provides the basis to define the potential added value of these markers in routine diagnosis and clinical trials of drugs targeting different pathomechanisms of AD.
