MAPT and early-onset autosomal dominant Alzheimer disease: Hyper-phosphorylation of the microtubule-associated protein Tau by microtubule affinity regulating kinase, the homolog of Drosophila Par-1 (MARK) [48], which is activated by upstream kinases, such as LKB1 [49] and Tao-1 [50], results in microtubule depolymerization and abnormal aggregation of Tau in Alzheimer disease.