Reactive astrogliosis: A friend or foe in the pathogenesis of Alzheimer’s disease

Abstract

Astrocytes are highly efficient homeostatic glial cells playing a crucial role in optimal brain functioning and homeostasis. Astrocytes respond to changes in brain homoeostasis following central nervous system (CNS) injury/diseased state by a specific defence mechanism called reactive astrogliosis. Recent studies have implicated and placed reactive astrogliosis in the centre of pathophysiology of Alzheimer's disease (AD) and other neurodegenerative disorders. The AD biomarker field is evolving rapidly with new findings providing strong evidence which supports the notion that a reactive astrogliosis is an early event in the time course of AD progression which may precede other pathological hallmarks of AD. Clinical/translational in vivo PET and in vitro postmortem brain imaging studies demonstrated ‘a first and second wave’ of reactive astrogliosis in AD with distinct close-loop relationships with other pathological biomarkers at different stages of the disease. At the end stages, reactive astrocytes are found to be associated, or in proximity, with amyloid plaque and tau pathological deposits in postmortem AD brains. Several new PET-tracers, which are being in pipeline and validated at a very fast pace for mapping and visualising reactive astrogliosis in the brain, will provide further invaluable mechanistic insights into AD and other non-AD dementia pathologies. The complementary roles of microglia and astrocyte activation in AD progression, along with the clinical value of new fluid astrocytes biomarkers in the context of existing biomarkers, are the latest avenue that needs further exploration.