Application of Artificial Neural Networks to Investigate One-Carbon Metabolism in Alzheimer’s Disease and Healthy Matched Individuals.docVIP

Application of Artificial Neural Networks to Investigate One-Carbon Metabolism in Alzheimer’s Disease and Healthy Matched Individuals Fabio Coppedè , Enzo Grossi , Massimo Buscema , Lucia Migliore 1* 2,3 3,4 1 1 Department of Translational Research and New Technologies in Medicine and Surgery, Division of Medical Genetics, University of Pisa, Pisa, Italy, 2 Bracco Foundation, Milan, Italy, 3 Semeion Research Center, Rome, Italy, 4 Department of Mathematical and Statistical Sciences, University of Colorado at Denver, Denver, Colorado, United States of America Abstract Folate metabolism, also known as one-carbon metabolism, is required for several cellular processes including DNA synthesis, repair and methylation. Impairments of this pathway have been often linked to Alzheimer’s disease (AD). In addition, increasing evidence from large scale case-control studies, genome-wide association studies, and meta- analyses of the literature suggest that polymorphisms of genes involved in one-carbon metabolism influence the levels of folate, homocysteine and vitamin B12, and might be among AD risk factors. We analyzed a dataset of 30 genetic and biochemical variables (folate, homocysteine, vitamin B12, and 27 genotypes generated by nine common biallelic polymorphisms of genes involved in folate metabolism) obtained from 40 late-onset AD patients and 40 matched controls to assess the predictive capacity of Artificial Neural Networks (ANNs) in distinguish consistently these two different conditions and to identify the variables expressing the maximal amount of relevant information to the condition of being affected by dementia of Alzheimer’s type. Moreover, we constructed a semantic connectivity map to offer some insight regarding the complex biological connections among th