However, it should be mentioned that, despite general beneficial role of Akt in neuronal survival, increased Akt activation and hyperphosphorylation of critical Akt substrates have been observed in AD brain, together with a significant loss and altered distribution of phosphatase and tensin homologue deleted in chromosome 10 (PTEN), the major negative regulator of Akt. The gene discussed is PTEN; the disease is Alzheimer disease.