Longevity & AgingCopper Overload Hijacks Microglia, Fueling Alzheimer's Inflammation
A new study reveals how sub-toxic copper accumulation worsens Alzheimer's-related neuroinflammation. Copper builds up in microglial mitochondria, depleting glutathione and generating oxidative stress. This releases oxidized mitochondrial DNA into the cytosol, activating the NLRP3 inflammasome and driving IL-1β and IL-18 secretion. Simultaneously, copper boosts cholesterol biosynthesis and its transport to mitochondria, downregulating ABCA7—a key receptor for amyloid-beta phagocytosis—so microglia can no longer clear toxic plaques effectively. Conditioned media from copper-overloaded microglia killed neurons, but this neurotoxicity was reversed by restoring mitochondrial glutathione or blocking the inflammasome, identifying promising therapeutic targets for Alzheimer's disease.
