Abstract
AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease that affects memory and cognition. Symptoms and onset of AD occur up to 20 years after potential alterations in biology, allowing for a tremendous potential to intervene in disease progression to change the AD course. In 2015, the National Plan to Address Alzheimer Disease as part of the National Alzheimer’s Project Act was signed into law which proposed to effectively prevent AD by 2025 sparking new interested in the clinical and research field to achieve these goals.MethodWe used a novel combination of text‐mining and natural language processing strategies to identify (i) AD risk factors, (ii) therapeutics that can target risk factor pathways and (iii) studies supporting therapeutics in the currently published PubMed database. To classify the literature relevant to AD preventive strategies, we developed a relevance score based on STRING score for protein‐protein interactions and a confidence score on Bayesian inference. This led to generation of a ranked list of candidate therapeutics to reduce AD risk.ResultBased on our strategy, 364 AD risk factors were identified mining 9,625 publications. Next, using drug databases, 694 FDA‐approved drugs were selected based on drug indications with a given risk factor. The computation of ranking scores enabled exclusion of publications that did not meet inclusion criteria and rank 45 drugs associated with reduced risk. Within this list, 22 therapeutics had at least one clinical study supporting AD risk reduction. The top 20 therapeutics included drugs within the categories of lipid‐lowering, anti‐inflammatory, anxiety/psychiatric, and metabolic‐related therapeutics.ConclusionOutcomes of our novel bioinformatic strategy supports therapeutic targeting of biological mechanisms and pathways underlying AD risk factors. Based on our analyses, we propose that early interventions that target pathways associated with increased risk of AD has the potential to achieve the goal of effectively preventing AD by 2025.
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