Background: Chronic inflammation is a feature of Alzheimer´s disease (AD), resulting in
excessive production of inflammatory mediators that can lead to neuroinflammation, contributing to
alterations in Aβ production and deposition as Senile Plaques (SPs), and to neurofibrillary tangles
(NFTs) formation, due to hyperphosphorylated Tau protein.
Objective: This work addressed the impact of the interleukin-8 (IL-8) and monocyte chemoattractant
protein-1 (MCP-1), two chemokines, on Tau phosphorylation; and also evaluated the chemokines’ levels
in plasma using samples from a regional cohort.
Methods: Human neuronal SH-SY5Y cells exposed to IL-8 and MCP-1 chemokines were monitored for
their protein and phosphorylated protein levels by western blotting analysis. A serine/threonine protein
phosphatase (PPs) activity assay was employed to monitor PPs activity. Subsequently, flow cytometry
was used to monitor chemokines levels in plasma samples from individuals with cognitive deficits.
Results: Chemokines’ exposure resulted only in minor cytotoxicity effects on SH-SY5Y, and in
increased Tau phosphorylation, particularly at the S396 residue. Tau phosphorylation correlated with
PPs inhibition and was consistent with GSK3β phosphorylation-mediated inhibition. Subsequent analysis
of plasma from individuals with cognitive deficits showed that IL-8 levels were decreased.
Conclusion: Data shows that both chemokines tested can exert an effect on GSK3β phosphorylation and
modulate PPs activity, potentially resulting in increased Tau phosphorylation and subsequent NFTs formation.
One can deduce that increased chemokines stimulation during chronic inflammation can exacerbate
this event. The work contributes to a better understanding of the mode of action of these chemokines
on AD pathogenesis and opens novel research avenues.