TTBK1 has been shown to co-localize with diffuse phospho-Ser422 tau in pre-tangle Alzheimer's disease neurons [52], and increased levels of TTBK1 have been observed in AD frontal cortex [53] and enhance the toxicity of tau in a P301L mouse model [54]. This evidence concerns the gene MAPT and early-onset autosomal dominant Alzheimer disease.