Furthermore, in the hippocampus and entorhinal cortex of AD patients, reactive astrocytes surrounding Aβ plaques have increased expression of neuronal nitric oxide synthase (nNOS), and neuronal DNA fragmentation roughly matches nNOS expression in astrocytes, indicating a causative role of NO-mediated oxidative damage in AD pathogenesis and interplay between OS and histopathological hallmarks of AD [41]. Here, NOS1 is linked to Alzheimer disease.