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Candidate Blood Proteome Markers of Alzheimer's Disease Onset and Progression: A Systematic Review and Replication Study

Research output: Contribution to journalLiterature reviewpeer-review

Steven J. Kiddle, Martina Sattlecker, Petroula Proitsi, Andrew Simmons, Eric Westman, Chantal Bazenet, Sally K. Nelson, Stephen Williams, Angela Hodges, Caroline Johnston, Hilkka Soininen, Iwona Kloszewska, Patrizia Mecocci, Magda Tsolaki, Bruno Vellas, Stephen Newhouse, Simon Lovestone, Richard J. B. Dobson

Original languageEnglish
Article numberN/A
Pages (from-to)515-531
Number of pages17
Issue number3
Early online date11 Oct 2013
E-pub ahead of print11 Oct 2013

King's Authors


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.

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