Unravelling Alzheimer’s Disease: Therapeutic Strategies Aimed at neuroinflammation signalling pathway

Abstract

Alzheimer’s disease (AD) is the most common progressive neurodegenerative disorder, character-ized by progressive cognitive decline and the accumulation of amyloid-β (Aβ) plaques and hyper-phosphorylated tau neurofibrillary tangles. Despite numerous clinical trials targeting disease mod-ification and neuroprotection, no therapy has consistently achieved its primary efficacy endpoints. This failure can be attributed to suboptimal study designs, an incomplete understanding of the dis-ease’s multifactorial molecular mechanisms, the paucity of reliable biomarkers, and confounding pharmacodynamic or pharmacokinetic effects. Beyond Aβ and tau pathology, neuroinflammation has emerged as a key driver in AD pathogenesis. Microglia and astrocytes, which play essential roles in neurotransmission and synaptic maintenance under homeostatic conditions, become aberrantly activated in AD. This shift leads to a chronic, self-perpetuating inflammatory response that aggra-vates Aβ and tau pathologies, thereby promoting synaptic dysfunction and neuronal loss. Con-sequently, targeting neuroinflammatory signaling pathways constitutes a promising therapeutic avenue. Modulating glial cell activity and interrupting pro-inflammatory cascades may modify disease progression and yield meaningful clinical benefits. This review explores current and emerging strategies focused on neuroinflammation, underscoring their potential to reshape the treatment landscape of AD.