Extensive studies of P301S mice further discovered synaptic pathology at 3 months of age, filamentous tau lesions and progressive tau accumulations in PFC, as well as cognitive impairment, at 6 months of age, neuronal loss and hippocampal and entorhinal cortical atrophy by 9–12 months of age [10, 15–19]. This evidence concerns the gene MAPT and Cognitive impairment.