Until recently, the diagnosis of AD was based on clinical and neuropsychological evaluations performed by a neurologist. However, Latest guidelines from Alzheimer´s Association and National Institute of aging (NIA)3, proposed a biological definition of AD based only in biomarkers, where a patient will be placed within the “AD continuum” depending on the results of tests that measure the brain accumulation of AB peptide, Tau and neurodegeneration. Although accurate tests from these biomarkers are available, most of them require invasive or expensive techniques, such as extraction of cerebrospinal fluid by lumbar puncture or neuroimaging.

As a consequence, these techniques cannot be prescribed to all patients and are not available in all medical centers, and there is a demand for cost-effective and simple tests that can reflect the alteration of those biomarkers in a non-invasive way.

Among other drawbacks, technical and logistical issues hamper the widespread application of these biomarkers in general clinical practice:

• They are expensive
• It’s required trained personnel to interpret the results
• They are not yet fully standardized/li>
• In some cases involve invasive procedures



The development of biomarkers that could be measured directly in blood would greatly facilitate the implementation and use of biomarkers for clinical diagnosis.

The failure during the last two decades of all experimental treatments led to the idea that treatments should be directed to prodromal or asymptomatic phases of the disease, making prevention AD a major objective in the AD Health strategy. As a matter of fact, AD prevention is the second major wave of preventive efforts in the field of neurology, after stroke.

Identification of people at risk is key for the effectiveness of preventative measures and consequently, APOE ε4 carriers were defined as a priority population where preventative treatments should be directed 4,5. Accordingly, several ongoing, prevention clinical trials include APOE ɛ4 as an inclusion factor (NCT02565511, NCT03131453, NCT02569398) and large-scale screening programs are being established to identify APOE ɛ4 carriers for AD preventive clinical trials.

e4Risk®, due to its simplicity, ease of use and cost-effective can be very useful as a screening test for AD clinical trials, where APOE ε4 carriers can be selected in a fast and inexpensive manner.

Intensive efforts are being place to define effective strategies to prevent or delay AD. Recently, it has been shown that multimodal intervention of modifiable vascular and life-style risk factors could improve or maintain cognitive functioning in at-risk elderly people7. Interestingly, this multimodal intervention consisting in diet, exercise, cognitive training and vascular risk monitoring has been shown effective also in APOE ɛ4 carriers8, suggesting that early detection of APOE ɛ4 carriers could be relevant for reducing AD prevalence through adoption of these vascular and life-style recommendations.