The multifaceted roles of IL-1β in Alzheimer's disease: From pathogenic amplifier to neuroimmune modulator.

Alzheimer's disease (AD) is a progressive age-related neurodegenerative disorder and the most common form of dementia worldwide. Traditionally, its pathology has been defined by the presence of extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs), primarily composed of hyperphosphorylated tau (pTau), alongside widespread synaptic and neuronal loss. Despite decades of research, AD etiology remains only partially understood. While recent advances in amyloid-targeted therapies mark significant progress, most current approaches have fallen short of expectations. This gap has spurred the re-evaluation of the central mechanisms driving AD, with neuroinflammation emerging as a critical contributor rather than a mere bystander. Among the numerous inflammatory mediators implicated in AD, interleukin-1β (IL-1β) stands out for its dual role, associated with the exacerbation of pathological features but also with neuroprotective effects, including Aβ clearance and neuronal support. This apparent duality highlights the complexity of neuroinflammation in AD, suggesting that IL-1β can act as a context-dependent modulator, its effects shaped by factors such as timing, cellular origin, and disease stage. The purpose of this review is to summarize the evidence on IL-1β's role in AD pathophysiology and clarify its contribution to disease mechanisms and progression.