Fig. 3: Conceptual framework for translating brain protein networks into clinical biomarkers.
From: Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau
In this framework, multidimensional discovery-driven proteomics data collected from local cell type-specific approaches and antemortem biofluids will be integrated with the AD brain network proteome to identify systems-based panels of promising CSF and/or plasma biomarkers. Target prioritization will rest on the significance, magnitude, reproducibility, and ease of detection of the candidate biomarker in disease. Prioritized targets will also require links to disease mechanisms, informed in part by localized and cell type-specific proteomics. These network-based biomarker panels will then be validated using targeted quantitation approaches, including mass spectrometry (MS) and immunoassays. Both validation methods offer highly sensitive and accurate quantitation, though MS may offer certain advantages, such as highly selective target detection using unique peptides and the ability to cost-effectively analyze large panels of proteins in an initial verification phase prior to more expensive validation efforts. Validated biomarker panels representing a wide range of pathophysiologies could serve a variety of clinical uses, including preclinical profiling, disease monitoring, measuring therapeutic response, and confirming target engagement.
