MAPT and Alzheimer disease: (2) TTBK1 can directly phosphorylate both tau [13] and TDP-43 [17] at phosphorylation sites enriched in the post-mortem tissue of AD (S422) and ALS (S409/S410) patients respectively (3) Using immunohistochemistry, TTBK1 protein has been shown to co-localize with both diffuse phosphorylated S422 tau in Alzheimer’s disease neurons [21] and immune-positive AT180 (Thr231) neurons in sections from the hippocampus of FTLD-tau patients [22].