Neuroinflammation in Alzheimer's disease:

Pathogenic Mechanisms and Therapeutic Implications

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia worldwide and is characterized by progressive cognitive decline associated with extracellular accumulation of beta-amyloid (Aβ) plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated Tau protein. Growing evidence indicates that neuroinflammation is not merely a secondary consequence of protein deposition but a central and dynamic driver of disease progression. This integrative review aims to critically analyze the pathogenic mechanisms of neuroinflammation in AD and discuss their therapeutic implications based on studies published between 2021 and 2025 in PubMed, SciELO, and LILACS databases. Findings demonstrate that chronic microglial activation, reactive astrocyte polarization, NLRP3 inflammasome activation, blood–brain barrier dysfunction, and peripheral immune–central nervous system interactions create a sustained neurotoxic microenvironment driven by pro-inflammatory cytokines and oxidative stress. These processes amplify amyloid deposition, promote Tau hyperphosphorylation, and precipitate synaptic dysfunction and neuronal loss. Preclinical evidence suggests that selective modulation of inflammatory pathways may reduce pathological burden and preserve cognitive performance, although translational challenges remain significant. Neuroinflammation emerges as an integrative axis in AD pathophysiology and a strategic therapeutic target requiring personalized approaches and validated inflammatory biomarkers for clinical application.