Neuroimmune dysregulation in Alzheimer's disease: Mechanisms and therapeutic strategies

Alzheimer's disease (AD) is a neurodegenerative disorder characterised by progressive memory loss and cognitive decline. With the global population ageing, the prevalence of AD continues to rise, posing a significant public health challenge. Historically, AD research has centred on two hallmark pathological features: β-amyloid (Aβ) deposition and tau protein hyperphosphorylation. However, repeated failures of therapeutic strategies targeting these pathways in clinical trials have prompted a paradigm shift toward a more integrated understanding of disease mechanisms. Accumulating evidence now demonstrates that neuroimmune dysfunction is not merely a secondary response but a central driver throughout AD progression, contributing to the initiation of pathology and perpetuating neuroinflammation, synaptic damage, and cognitive deterioration. This review highlighting the primary pathways involved in inflammation and neuroimmune dysregulation in AD, and the role of gut microbiota dysbiosis and systemic immunity in the pathogenesis. Furthermore, it discusses emerging neuroimmune-targeted intervention strategies such as activation of TREM2, CD33 antagonists or antisense oligonucleotides, aiming to provide a conceptual foundation for broadening mechanistic insights and guiding the development of novel therapeutic approaches.