 Neurodegenerative diseases, such as Alzheimer's disease, are caused by poorly understood factors including neuroinflammation and oxidative stress. These factors contribute to disease progression and can activate disease-associated microglia, DAM, through damage-associated molecular patterns, DAMPs. This leads to the production of reactive oxygen species, ROS, and protein aggregation, resulting in neuronal damage and the activation of DAM. The molecular mechanisms linking DAM activation and oxidative stress have not yet been fully defined, so targeting these cells for clinical benefit has not been possible. In microglia, ROS are produced primarily by NADPH oxidase II, NOX2, and activation of NOX2 in DAM is associated with DAMP signaling, inflammation and amyloid plaque deposition, especially in the cerebrovascular. Additionally, ROS originating from both NOX and the mitochondria may act as second messengers to propagate immune activation, thus intracellular ROS signaling may underlie excessive inflammation and oxidative stress. Targeting This article was offered by Dominic S. A. Simpson and Peter L. Oliver. We are article.tv, links in the description below.