MAPT and Alzheimer disease: The early appearance of tau-ir neurons in the forebrain of 3xTg-AD mice is not surprising since overexpression of mutant P301L four repeat tau and the APPswe amyloid mutation together [59] or tau P301L alone [60] induces an age dependent onset of MC1, AT8, and PHF-ir neurofibrillary tangles (NFTs) in the telencephalon of mutant mice as young as 2.5 months of age [60].