Treatment with Interleukin-17A antibody restored behavioral and neuronal biomarkers in Amyloid-beta1--42-exposed model of Alzheimer's disease.

The neuroinflammation in Alzheimer's disease (AD) is due to amyloid-beta1-42 (Aβ1-42) triggered cytokines release from the brain resident immune cells. Interleukin-17A (IL-17A) is one of the crucial cytokines involved in orchestrating neuroinflammation and exacerbating AD pathology. Thus, IL-17A may be considered as one of the key therapeutic options to control AD progression. This study was conducted using BALB/c mice divided into four groups, such as control group, Aβ1-42 (5 μg) group, Aβ1-42 (5 μg) + IL-17A neutralizing antibody (1 μg) group, and Aβ1-42 (5 μg) + antibody control (IgG1 isotype, 1 μg) group. The intranasal exposure of either Aß1-42 or vehicle was administered once daily for the first seven consecutive days. The intranasal exposure to anti-mouse IL-17A neutralizing antibody or isotype control was performed once daily from day 5 to day 7, one hour after Aß1-42 exposure. The memory evaluations were conducted through the Morris water maze, novel object recognition test, and passive avoidance test. The brain IL-17A cytokine levels were increased >2-fold in Aβ1-42-exposed mice as compared to control. IL-17A antibody exposure led to significant partial improvement in cognitive memory and significantly reduced the expression of AD biomarkers (amyloid precursor protein, beta secretase, phosphorylated tau) along with a significant suppression of IL-17A signaling axis, astrogliosis, neuronal damage and cytokines in the brain regions of Aβ1-42-exposed animals. In conclusion, neutralizing IL-17A prevented Aβ1-42-mediated effects and revealed IL-17A as a potential therapeutic target involved in the regulation of AD progression and pathology.