MAPT and Alzheimer disease: Challenges surrounding AD drug discovery include mis-diagnosis of clinical trial patients [10,11,12], a lack of reliable biomarkers [10], and an incomplete understanding of the complex and multifaceted disease pathology involving tau hyper-phosphorylation, Aβ aggregation, cholinergic dysfunction, metal dysregulation, inflammation, and oxidative stress [3,6,13,14], which are often interconnected.