Longevity & AgingNAD+ Depletion in Brain Blood Vessels Sparks Alzheimer's Neuroinflammation
Researchers discovered that amyloid beta (Aβ) depletes NAD+ in brain endothelial cells (BECs), causing mitochondrial DNA to leak into the cytosol and activate the cGAS/STING innate immune pathway. This cascade drives endothelial senescence, upregulates the NAD+-consuming enzyme CD38, and promotes a pro-inflammatory SASP that activates microglia via IL-6 signaling. In APP/PS1 Alzheimer's mice, supplementation with nicotinamide riboside (NR) restored NAD+ levels, suppressed cGAS/STING signaling, reduced neuroinflammation, improved vascular integrity, and rescued cognitive function—pointing to vascular NAD+ restoration as a compelling therapeutic strategy for Alzheimer's disease.
