Inflammation and the pathophysiology of Alzheimer's disease.
There is increasing evidence that a chronic inflammatory response in the brain in Alzheimer's disease (AD) ultimately leads to neuronal injury and cognitive decline. Microglia, the primary immune effector cells of the brain, are thought to be key to this process. This paper discusses the evidence for inflammation in AD, and describes the mechanism whereby microglia generate neurotoxic cytokines, reactive oxygen species, and nitric oxide. Evidence that the cytokine macrophage colony-stimulating factor (M-CSF) is an important cofactor in microglial activation in AD is presented. Ongoing work using organotypic hippocampal expiant cultures to model the inflammatory process in the AD brain is also discussed. Potential avenues for therapeutic intervention are outlined.
Neuroscience Research Laboratories, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif, USA.
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Greer