Biomarkers for Alzheimer’s disease: Not Necessarily Desirable but Definitely Essential

Alzheimer’s disease is a devastating disorder – to individuals, to families and, as it costs the state more than heart disease and cancer combined, to health services and potentially economies. As life gets longer, things are going to get only worse as more people live to the age of risk. Balanced against this gloomy scenario is the considerable progress made in the last two decades towards an understanding of the molecular pathogenesis of the disease and the rational design of drugs to slow or even halt progression. And here’s the rub – Alzheimer’s has a prodromal or preclinical phase that might be as long as ten or more years. Treat the disease in that phase and there is every possibility that effective treatment will equate to clinical prevention. But in order to treat the disease in this phase, then biomarkers of this preclinical pathology are needed. As conventional trials of disease modification agents in established disease are failing, the options in Alzheimer’s disease are becoming stark: either we will have markers enabling precision medicine in clinically unaffected individuals or we will have nothing.

In the search for such preclinical biomarkers most progress has been made in measuring candidate markers, particularly amyloid, using CSF as a test-fluid for immunocapture assays, and molecular PET imaging as an imaging technology. Studies compare people with dementia to those without. As an alternative approach we have been using proteomics and genomics rather than candidates, using blood as a test-fluid and, most important, using a study design focusing on trying to identify biomarkers of pathology rather than biomarkers of clinical disease. Using these approaches we have found a set of genes and proteins that have accuracy in the utility range for diagnosis and have some evidence for very early, or even pre-clinical, detection.

These findings have the potential to change our perspectives on Alzheimer’s disease and as a consequence we are changing our services for assessing people with dementia. Gearing up for an era of personalized medicine, at King’s Health Partners we are streamlining assessment and scaling data collection through the electronic medical records coupled to routine collection of samples.