Interleukin-17 (IL-17) triggers systemic inflammation, peripheral vascular dysfunction, and related prothrombotic state in a mouse model of Alzheimer's disease

Alzheimer's disease (AD) is one of the most prevalent forms of neurodegenerative disorders. Previously, we have shown that in vivo administration of an IL-17 neutralizing antibody (IL-17Ab) rescues amyloid‐β‐induced neuro-inflammation and memory impairment, demonstrating the pivotal role of IL-17 in AD-derived cognitive deficit. Recently, AD has been recognized as a more intriguing pathology affecting vascular networks and platelet function. However, not much is known about peripheral vascular inflammation and how pro-inflammatory circulating cells/mediators could affect peripheral vessels’ function. This study aimed to evaluate whether IL‐17Ab treatment could also impact peripheral AD features, such as systemic inflammation, peripheral vascular dysfunction, and related pro-thrombotic state in a non-genetic mouse model of AD. Mice were injected intracerebroventricularly with Aβ1–42 peptide (3 μg/3 μl). To evaluate the systemic/peripheral protective profile of IL-17Ab, we used an intranasal administration of IL-17Ab (1 μg/10 μl) at 5, 12, and 19 days after Aβ1–42 injection. Circulating Th17/Treg cells and related cyto-chemokines, haematological parameters, vascular/endothelial reactivity, platelets and coagulation function in mice were evaluated. IL-17Ab treatment ameliorates the systemic/peripheral inflammation, immunological perturbance, vascular/endothelial impairment and pro-thrombotic state, suggesting a key role for this cytokine in fostering inflammatory processes that characterize the multifaced aspects of AD. [Display omitted] •Alzheimer's disease onset and progression are sustained by IL-17 with an impact on systemic/peripheral inflammation, endothelial impairment, and pro-aggregative state.•Administration of a neutralizing-IL‐17A antibody rescues AD-related systemic/peripheral immunological and inflammatory-based disfunction of AD.•The non-genetic mouse model of Aβ1–42-induced Alzheimer's disease recapitulates the main features of pathology.