Neutralization of interleukin-17 rescues amyloid-β-induced neuroinflammation and memory impairment.

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is a common neurodegenerative disease characterized by a neuroinflammatory state and to date, there is no cure and its treatment represents a large unmet clinical need. The involvement of T helper 17 cells in the pathogenesis of AD-related neuroinflammation has been reported in several studies, however the role of the main cytokine, IL-17, has not been well addressed. Herein, we investigate the effects of IL-17 neutralizing antibody (IL-17Ab) injected by intracerebroventricular (ICV) or intranasal (IN) routes on amyloid-β-induced neuroinflammation and memory impairment in mice.

EXPERIMENTAL APPROACH: Amyloid-β (Aβ)1-42 was injected into cerebral ventricle of adult CD1 mice. These mice received IL-17Ab via ICV either at 1 hour prior to Aβ1-42 injection or IN 5 and 12 days after Aβ1-42 injection. After 7- and 14-days of Aβ1-42 administration, we evaluated olfactory, spatial and working memory and performed biochemical analyses on whole brain and specific brain areas.

KEY RESULTS: Remarkably, ICV pre-treatment with IL-17Ab remarkably reduced Aβ1-42 -induced neurodegeneration, improved memory function and prevented the increase of pro-inflammatory mediators in a dose dependent manner at 7- and 14-days. Similarly, the double IN administration of IL-17Ab after Aβ1-42 injection reduced neurodegeneration, memory decline and the levels of pro-inflammatory mediators and cytokines.

CONCLUSION AND IMPLICATIONS: These findings suggest that IL-17Ab reduces neuroinflammation and behavioral symptoms induced by Aβ. The efficacy of IL-17Ab IN administration in reducing Aβ1-42 neurodegeneration points to a possible future therapeutic approach in patients with AD.