Interleukins in Alzheimer's Disease: Mechanisms, Biomarkers, and Therapies

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disorder in which long-term brain inflammation interacts with amyloid-β (Aβ) and tau abnormalities, leading to synaptic damage and cognitive decline. Interleukins are important in this process because they connect glial activation, harmful protein accumulation, and neuronal injury. Although recent studies have identified inflammatory pathways and blood cytokine patterns associated with AD, their roles at different stages and their clinical value remain unclear. This review discusses interleukin-related inflammation, inflammatory biomarkers, and developing immune-regulating treatments for AD. It describes how microglia change from protective cells that clear harmful substances into overactivated cells that may increase damage; the NLRP3–caspase-1 pathway is also presented as a link between Aβ or tau stress and IL-1β/IL-18 release. IL-6, IL-17A, IL-7, and IL-15 are examined within wider immune networks, as combined inflammatory patterns may be more closely related to cognition and nerve fiber injury than single cytokines. Treatments involving NLRP3, TREM2, CD33, TNF-related pathways, natural products, diet, gut microbiota, and lifestyle are also reviewed; combination therapy may be suitable because AD varies among patients. Current findings support a move from general anti-inflammatory treatment toward stage-based, biomarker-guided immune regulation, which may reduce cytokine damage while maintaining microglial clearance and repair. However, causal links, suitable treatment periods, and reliable brain-specific inflammatory markers remain uncertain; future studies should use long-term multimodal cohorts, human-relevant models, and grouped clinical trials combining cytokine patterns with Aβ, tau, NfL, GFAP, genetics, and neuroinflammatory imaging.