Histopathological studies of the brains of cognitively normal octogenarians, nonagenarians and centenarians have shown that essentially all very old subjects exhibit one or more neuropathological features, with many having levels of Aβ plaques and p-Tau sufficient for a diagnosis of AD.31,32 On the other hand, some subjects may have only modest amounts of Aβ plaques and p-Tau pathology and yet exhibit robust neuronal loss and cognitive impairment. This evidence concerns the gene MAPT and Alzheimer disease.