NEUROINFLAMMATION AND NEURODEGENERATION IN ALZHEIMER’S DISEASE: A MODERN REVIEW

Abstract

Alzheimer's disease (AD) is the most prevalent cause of dementia and represents a major global health challenge due to its increasing incidence and lack of effective disease-modifying therapies. While the classical pathological hallmarks of AD include extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein, growing evidence indicates that neuroinflammation is a critical driver of disease onset and progression. Persistent activation of microglia and astrocytes, dysregulation of the innate immune response, excessive production of pro-inflammatory cytokines, oxidative stress, mitochondrial dysfunction, and blood–brain barrier impairment collectively contribute to synaptic dysfunction and progressive neuronal loss. Recent advances in molecular biology have identified several inflammatory signaling pathways, including nuclear factor kappa B (NF κB), NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, complement cascade, and triggering receptor expressed on myeloid cells-2 (TREM2), as promising therapeutic targets. Furthermore, novel therapeutic approaches involving monoclonal antibodies, small-molecule inhibitors, stem cell therapy, nanotechnology-based drug delivery systems, and natural bioactive compounds have demonstrated encouraging neuroprotective and anti-inflammatory effects in preclinical and clinical studies. Emerging biomarkers based on neuroimaging, cerebrospinal fluid, blood-derived inflammatory mediators, and genetic profiling are also improving the early diagnosis and monitoring of disease progression. This review comprehensively discusses the molecular mechanisms linking neuroinflammation and neurodegeneration in AD, summarizes recent advances in diagnostic biomarkers and therapeutic interventions, and highlights current challenges and future perspectives in the development of targeted strategies to delay disease progression and improve patient outcomes.