APOE and Alzheimer disease: This is one of the largest non-targeted plasma studies to date to use such a systematic analysis pipeline, which included assessment of the model in an independent data set (1/3 of sample), to identify new targets linked to AD and provide improvement to current diagnostic classifiers.11, 12, 13, 14, 15, 16 Although APOE was associated with AD in single analyte analyses, its variable importance in the presence of the metabolites during classification was low and was not included in the classifier probably due to the metabolites already capturing the information that APOE provides.