Proteomic and metabolomic biomarkers of Alzheimer’s disease: Opportunities to advance precision medicine and clinical trials

Medical advances that prolong the lifespan of people with Down Syndrome (DS) have led to increasing incidence of age-related diseases such as Alzheimer’s Disease (AD). The scientific community is aggressively working to develop valid and reliable biomarkers of AD that are low cost, noninvasive, and intuitive. It is critical that these biomarkers accurately reflect the heterogeneity of people affected by AD, either those in the general population or those with specific risk factors such as people with DS. Within the framework of systems biology, the proteome and metabolome are most proximate to the endophenotype, thus biomarkers from these omics levels may provide highly accurate information for diagnosis and more precise temporal information for predicting phenoconversion events. These biomarkers would be invaluable for precision medicine and for upcoming clinical trials, useful for enriching participant pools and serving as markers of target engagement, and primary endpoints. Standardization of preanalytical sources of biological noise such as biofluid collection and processing pipelines, and protein and metabolite quantification approaches are hurdles that still need to be overcome.