Beyond Neuroinflammation: Microglia at the Crossroads of Amyloid, Tau, and Neurodegeneration in Alzheimer’S Disease Publisher



R Ebrahimi RASOUL ; S Bordbar SANAZ ; G Azad GHAZAL ; S Davoody SAMIN ; Ms Mahmoudi Mah SIMA ; K Esmaeilpourbezenjani K
Source: Neurological Sciences Published:2025

Abstract

Microglia, the brain’s resident immune cells, are increasingly recognized as central players in the complex landscape of Alzheimer’s disease (AD). Traditionally associated with neuroinflammation, their roles extend far beyond, touching nearly every aspect of disease progression—from amyloid β (Aβ) and tau pathology to synaptic integrity and cognitive function. While early studies focused on their inflammatory responses, recent findings highlight a more nuanced picture: microglia can both protect and harm, depending on their state and the disease context. In this review, we examine the diverse functions of microglia at the crossroads of Aβ and tau pathology, emphasizing how dysfunction in their regulatory and clearance mechanisms can exacerbate neurodegeneration. We also explore how these insights are shaping therapeutic strategies aimed at modulating microglial activity to preserve brain health. By broadening the focus beyond inflammation alone, this work presents a more integrated view of microglial involvement in AD pathogenesis. © 2025 Elsevier B.V., All rights reserved.