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The contribution of chronic peripheral inflammation to the pathogenesis of neurodegenerative diseases is an outstanding question.Sustained activation of the peripheral innate and adaptive immune systems occurs in the context of a broad array of disorders ranging from chronic infectious diseases to autoimmune and metabolic diseases.In addition,progressive systemic inflammation is increasingly recognized during aging.Peripheral immune cells could potentially modulate the cellular brain environment via the secretion of soluble molecules.There is an ongoing debate whether peripheral immune cells have the potential to migrate into the brain under certain permissive circumstances.In this perspective,we discuss the possible contribution of chronic peripheral inflammation to the pathogenesis of age-related neurodegenerative diseases with a focus on microglia,the resident immune cells of the brain parenchyma.