Biochemical analysis using anti-tau antibodies for phosphorylated Ser 202 (CP13) and Ser 202/Thr205 (AT8) present in early (pre-tangles) and advanced NFTs, and Ser 396/404 (PHF-1), a marker of late NFT stages in AD brain (Table 1), revealed enhanced tau phosphorylation in the cortex and hippocampus of PS cKO mice (Fig. 2a, b). This evidence concerns the gene PHF1 and Alzheimer disease.