Identification of Optimum Panel of Blood-based Biomarkers for Alzheimer's Disease Diagnosis Using Machine Learning

With the increasing number of people living with Alzheimer's disease (AD), there is a need for low-cost and easy to use methods to detect AD early to facilitate access to appropriate care pathways. Neuroimaging biomarkers (such as those based on PET and MRI) and biochemical biomarkers (such as those based on CSF) are recommended by international guidelines to facilitate diagnosis. However, neuroimaging is expensive and may not be widely available and CSF testing is invasive. Bloodbased biomarkers offer the potential for the development of a low-cost and more time efficient tool to detect AD to complement CSF and neuroimaging as blood is much easier to obtain. Although no single blood biomarker is yet able to detect AD, combinations of biomarkers (also called panels) have shown good results. However, a large number of biomarkers are often needed to achieve a satisfactory detection performance. In addition, it is difficult to reproduce reported results within and across different study cohorts because of data overfitting and lack of access to the datasets used in the studies. In this study, our focus is to identify an optimum panel (in terms of the least number of blood biomarkers to meet the specified diagnostic performance of 80% sensitivity and specificity) based on a widely accessible data set, and to demonstrate a testing methodology that reinforces reproducibility of results. Realizing a panel with reduced number of markers will have significant impact on the complexity and cost of diagnosis and potential development of cost-effective point of care devices.