In the context of an ageing population, the prevalence of neurodegenerative diseases is increasing worldwide; the estimated 46.8 million people worldwide living with dementia in 2015 will rise to 131.5 million by 2050. Alzheimer's disease is the most common cause of dementia, resulting in a gradual decline in cognitive function in sufferers. Current treatment options are limited to the alleviation of symptoms or the introduction of lifestyle or dietary adjustments aimed at slowing down disease progression, with no cure available.
In an effort to develop a deeper understanding of the disease, over a decade of research has established the physical basis for beta-amyloid-rich plaques, toxic accumulation of the tau protein in neurofibrillary tangles or the inflammatory components of Alzheimer's disease. Impaired clearance of lipid deposits in the brain tissue involving apoliprotein E (ApoE) is implicated in each of these phenomena, and accordingly, the ApoE4 variant of this gene is recognised as one of the most powerful genetic risk factors for dementia and other neurodegenerative diseases.
As we enter an era of personalised medicine, screening for the ApoE4 variant is a consideration to allow those who choose this option to employ lifestyle adjustments, health monitoring, available countermeasures or to otherwise plan their lives accordingly.
Further, within the clinical trial industry, ApoE4 status is recommended for screening of subjects when investigating new therapeutics so that specific at-risk ApoE4 carrier populations can be identified. Patient advocate and peer support groups are emerging for those identified with ApoE4 carrier status to assist with the implications of learning one's status in addition to promoting the search for better outcomes for those living with Alzheimer's.
Emerging therapeutic strategies, including targeting the facets of Alzheimer's disease pathology in large scale clinical trials, have met with difficulties that include a lack of efficacy of promising preclinical drug candidates. Opinions differ as to the cause of these failures; either trials are being conducted on patients whose disease is too well established to benefit from the study drug, too narrow a focus on one aspect of the disease or perhaps the need for identification of the appropriate patients that would benefit. Taken together, a test for identification of ApoE4 carrier status that is rapid, cost-effective and easily implementable is highly desirable.
Presently, Molecular approaches are employed to determine a patient's ApoE genotype, using PCR of genomic DNA samples obtained from the subject. This process requires informed consent for sample collection, DNA extraction and analysis of genetic information, and specialised equipment not readily available or practicable in a routine clinical laboratory setting.
The Randox Biochip Array Technology (BAT) platform offers a potential solution through immunoassay plexing that allows direct identification of ApoE4 carrier status from a plasma sample. The ApoE4 Biochip identifies susceptible individuals through simultaneous chemiluminescent sandwich immunoassays for measurement of ApoE4 and total ApoE. This assay can be implemented through the highly versatile Evidence series of biochip analysers, from small laboratory to high throughput systems. Using the Evidence Investigator, the time from sample acquisition to result may be as little as three hours. Using the fully automated Evidence Evolution platform, a throughput of one sample per minute can be achieved along with the elimination of the sample handling requirements associated with PCR-based methods. Validation of the biochip-based ApoE4 genotyping assay has demonstrated complete concordance with PCR-based reference methods.
In conjunction with other emerging biomarkers, the ApoE4 array promises to be of major benefit for future diagnosis, risk monitoring and therapeutic targeting of Alzheimer's disease. With approximately 2,000 registered trials in Alzheimer's disease on ClincalTrials.gov - featuring monitoring and therapeutic intervention strategies - a rapid, efficient means of ApoE4 carrier status is not only essential, but is now available.