Whilst there are reports that NUAK1 levels may be upregulated [37] and tau is phosphorylated at Ser356 in end-stage AD [3, 18, 26, 27, 64], the progression of p-tau Ser356 accumulation over the disease time course, its representation in tangles and its association with synapses (synaptic tau has been found to be important for both tau toxicity and trans-synaptic tau spread [9, 36, 47, 68]) have not been fully characterised. This evidence concerns the gene MAPT and Alzheimer disease.