Therefore, in MCI brain, dysfunctional Pin1 no longer regulates APP and phosphorylated tau, consistent with the concept that dysfunctional Pin1 contributes to formation of the two principal hallmarks of MCI (and AD) neuropathology, senile plaques that are rich in highly aggregated Aβ42 fibrils, and hyperphosphorylated tau-containing neurofibrillary tangles. This evidence concerns the gene PIN1 and Alzheimer disease.