In this respect, in a recent study, we found a conspicuous abnormal phosphorylation of tau in the typical thorny excrescences of hippocampal CA3 neurons in a pre-tangle state (pattern I, see below), which was independent of the stage of AD pathology and of the intensity of the phosphotau immunostaining in the DG (Blazquez-Llorca et al., 2011; Figure 3). This evidence concerns the gene MAPT and Alzheimer disease.