Blood based biomarkers for Alzheimer’s disease – from case control to endophenotype discovery and from small to large, potentially huge, replication

Simon Lovestone1,*

1Department of Psychiatry, University of Oxford, Oxford, United Kingdom

Alzheimer’s disease is a common and invariably progressive disorder which incurs huge costs to families as well as health systems and for which there is no disease modifying therapy. Although progress has been made in understanding the pathogenesis of the condition, trials based on this understanding are repeatedly failing. One reason for this might be that trials are conducted too late in the disease process. AD has a prodromal period of a decade or more and performing trials in this period might enable compounds to show efficacy. However, in order to test this hypothesis, means are needed to detect disease before it is fully established.

Biomarkers are therefore critical to the development of therapeutics. We have sought such markers in blood first using case control design and increasingly using endophenotype based approaches. In both we have employed mass spectrometry driven proteomics (gel based and gel free) as well as protein arrays and targeted confirmation by validation and replication. These studies have shown that there is a signal indicative of disease in AD, that some of the markers identified suggest possible therapeutic targets and that at least some of the putative markers are replicated across studies and analytical platforms.


However, in order to demonstrate research utility, let alone clinical utility, considerably larger replication studies are required. With cross national pre-competitive studies such as the European Medical Information Framework as well as national studies such as the UK Dementias Platform, we are now in a good position to perform the replication analyses necessary to progress peripheral biomarkers for Alzheimer’s disease.

Keywords: Biomarker, Blood, Brain