MAPT and Alzheimer disease: Aβ oligomers in cultured hippocampal neurons lead to phosphorylation of tau and inhibition of IRS-1 (Ser616) through the activation of c-Jun N-terminal kinase signalling, while curcumin treatment of triple transgenic -AD mice on a high-fat diet showed reductions in phosphorylated JNK, IRS-1, and tau in their brain [261].