Basic Science and Pathogenesis

Neuroinflammation in Alzheimer's disease (AD) plays a critical role in inducing cellular injury and exacerbating disease pathology. Among the proinflammatory cytokines, interleukin-17A (IL-17A) has been significantly associated with AD, amplifying neuroinflammation during disease progression.

This study explored the role of IL-17A in exacerbating amyloid-beta (Aβ)-induced pathology. AD pathology in mice was induced through repeated intranasal administration of Aβ alongside recombinant mouse IL-17A (rmIL-17) at doses of 1, 2, and 4 µg/kg for seven alternate days.

While combining rmIL-17 with Aβ did not severely impact memory when compared to Aβ, it markedly intensified IL-17A-mediated signaling. This combination elevated proinflammatory cytokines, increased oxidative stress, and reduced antioxidant levels in the hippocampus and cortex. Interestingly, the co-administration of rmIL-17 and Aβ also upregulated key AD structural markers, including pTau, amyloid-beta, and BACE1, in the brain regions. Furthermore, it activated astrocytes and microglia, leading to a shift in microglial polarization from anti-inflammatory to pro-inflammatory states.

These findings highlight the potential of IL-17A to aggravate AD pathology and emphasize its significance as a therapeutic target for controlling disease progression.