MAPT and Cognitive impairment: This evidence of a crucial role of tau in synaptotoxicity is supported by the observation that hyperphosphorylated tau accumulates in dendritic spines of cultured CA3 hippocampal neurons [41, 112], and the finding that crossing human APP transgenic mice with human tau transgenic mice causes an enhanced aggregation of tau with concomitant dendritic spine loss, and accelerates cognitive impairment [20].