Recent genetic studies suggest a central role for innate immunity in Alzheimer's disease (AD) pathogenesis, wherein microglia orchestrate neuroinflammation. Kv1. 3, a voltage-gated potassium channel of therapeutic relevance in autoimmunity, is upregulated by activated microglia and mediates amyloid-mediated microglial priming and reactive oxygen species production in vitro. We hypothesized that Kv1. 3 channel expression is increased in human AD brain tissue. In a blinded postmortem immunohistochemical semi-quantitative analysis performed on ten AD patients and ten non-disease controls, we observed a significantly higher Kv1. 3 staining intensity (p= 0.03) and Kv1. 3-positive cell density (p= 0.03) in the frontal cortex of AD brains, compared to controls. This paralleled an increased number of Iba1-positive microglia in AD brains. Kv1. 3-positive cells had microglial morphology and were associated with amyloid-β plaques. In immunofluorescence studies, Kv1. 3 channels co-localized primarily with Iba1 but not with astrocyte marker GFAP, confirming that elevated Kv1. 3 expression is limited to microglia. Higher Kv1. 3 expression in AD brains was also confirmed by western blot analysis. Our findings support that Kv1. 3 channels are biologically relevant and microglia-specific targets in human AD.