IL-17 A Exacerbated Neuroinflammatory and Neurodegenerative Biomarkers in Intranasal Amyloid-Beta Model of Alzheimer's Disease.

Abstract

Proinflammatory cytokines, especially interleukin-17 A (IL-17 A) have been found to be significantly associated with AD patients. IL-17 A amplifies neuroinflammation during AD pathology. This study highlighted the ability of IL-17 A to exacerbate amyloid-beta-induced pathology in animals. The AD pathology was induced with repeated intranasal administration of Aβ along with recombinant mouse IL-17 A (rmIL-17) at 1, 2 and 4 µg/kg for seven alternate days. Although, the combination of rmIL-17 and Aβ did not have severe effects on memory of the animals, but it drastically increased the IL-17 A mediated signaling, level of proinflammatory cytokines, oxidative stress and reduced antioxidants in the hippocampus and cortex regions of the animal brains. Interestingly, combining rmIL-17 with Aβ also triggered the expression of AD structural markers like pTau, amyloid-beta and BACE1 in the brain regions. Furthermore, rmIL-17 with Aβ exposure stimulated astrocytes and microglia leading to activation of proinflammatory signaling in the brain of the animals. These results showed the propensity of IL-17 A to promote severity of AD pathology and suggest IL-17 A as potent therapeutic target to control AD progression.