Targeting inflammaging in Alzheimer’s disease: molecular pathways and emerging pharmacotherapies

Abstract

Alzheimer’s disease (AD), the leading cause of dementia, is intrinsically linked to the aging process. A central mechanism driving this association is inflammaging, a state of chronic, low-grade inflammation resulting from innate immune dysregulation. Emerging evidence suggests that inflammaging is not merely a background feature of aging but an active pathogenic driver of AD, accelerating amyloid-β accumulation, tau hyperphosphorylation, and synaptic failure. This review synthesizes the molecular circuitry connecting inflammaging to AD, detailing the synergistic roles of the NLRP3 inflammasome, impaired autophagy, TREM2 signaling, and the cGAS-STING pathway. Furthermore, we critically evaluate pharmacological strategies designed to disrupt these cascades, including specific NLRP3 inhibitors, senolytic agents, and autophagy enhancers. We propose that these therapies offer a vital complementary approach to amyloid-targeting treatments, potentially modifying disease progression by extinguishing the persistent inflammatory milieu of the aging brain.