A blood-based
protein biomarker, or set of
protein biomarkers, that could predict onset and progression of
Alzheimer's disease (AD) would have great utility; potentially clinically, but also for clinical trials and especially in the selection of subjects for preventative trials. We reviewed a comprehensive list of 21 published discovery or panel-based (> 100
proteins) blood proteomics studies of AD, which had identified a total of 163 candidate
biomarkers. Few putative blood-based
protein biomarkers replicate in independent studies but we found that some
proteins do appear in multiple studies; for example, four candidate
biomarkers are found to associate with AD-related phenotypes in five independent research cohorts in these 21 studies: α-1-antitrypsin, α-2-macroglobulin,
apolipoprotein E, and
complement C3. Using SomaLogic's SOMAscan proteomics technology, we were able to conduct a large-scale replication study for 94 of the 163 candidate
biomarkers from these 21 published studies in plasma samples from 677 subjects from the AddNeuroMed (ANM) and the Alzheimer's Research UK/Maudsley BRC
Dementia Case Registry at King's Health Partners (ARUK/DCR) research cohorts. Nine of the 94 previously reported candidates were found to associate with AD-related phenotypes (False Discovery Rate (FDR) q-value < 0.1). These
proteins show sufficient replication to be considered for further investigation as a
biomarker set. Overall, we show that there are some signs of a replicable signal in the range of
proteins identified in previous studies and we are able to further replicate some of these. This suggests that AD pathology does affect the blood
proteome with some consistency.