Additionally, STEP61 protein levels are progressively increased in the cortex of Tg2576 mice over the first year, as well as in the prefrontal cortex of human AD brains [42], suggesting that NR2B subunit dephosphorylation and endocytosis might be important regulatory mechanisms that lead to neuronal dysfunction and damage during the progression of AD. This evidence concerns the gene PTPN5 and Alzheimer disease.