Neurobiology of Stress, Volume 9, November 2018,
Microglia are the predominant immune cells of the central nervous system (CNS) that exert key physiological roles required for maintaining CNS homeostasis, notably in response to chronic stress, as well as mediating synaptic plasticity, learning and memory. The repeated exposure to stress confers a higher risk of developing neurodegenerative diseases including sporadic Alzheimer's disease (AD). While microglia have been causally linked to amyloid beta (Aβ) accumulation, tau pathology, neurodegeneration, and synaptic loss in AD, they were also attributed beneficial roles, notably in the phagocytic elimination of Aβ. In this review, we discuss the interactions between chronic stress and AD pathology, overview the roles played by microglia in AD, especially focusing on chronic stress as an environmental risk factor modulating their function, and present recently-described microglial phenotypes associated with neuroprotection in AD. These microglial phenotypes observed under both chronic stress and AD pathology may provide novel opportunities for the development of better-targeted therapeutic interventions.
Alzheimer Disease; Alzheimer's Disease; Amyloid Beta Protein; Amyloidosis; Anxiety; Apoptosis; Brain Derived Neurotrophic Factor; Cardiovascular Disease; Chemotaxis; Chronic Stress; Cognitive Defect; Dark Microglia; Dementia; Depression; Down Regulation; Gene Expression; Human; Interleukin 10; Interleukin 6; Messenger RNA; Microglia; Microglial Phenotypes; Nerve Cell Plasticity; Nerve Degeneration; Nervous System Inflammation; Neurodegeneration; Neuroinflammation; Neuroprotection; Nonhuman; Oxidative Stress; Phagocytosis; Phenotype; Priority Journal; Protein Degradation; Protein Expression; Protein Phosphorylation; Reactive Oxygen Metabolite; Review; Risk Factor; Stress; Synaptic Remodeling; Tumor Necrosis Factor; Upregulation; Global