title: Potassium channel Kv1.3 is highly expressed by microglia in human Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Neurology, Emory University, Atlanta, GA, USA.
authors.forename: Srikant
authors.initials: S
authors.lastname: Rangaraju
authors.affiliation: Department of Neurology, Emory University, Atlanta, GA, USA.
authors.forename: Marla
authors.initials: M
authors.lastname: Gearing
authors.affiliation: Department of Pathology and Laboratory Medicine, Alzheimer's Disease Center, University of California Davis, CA, USA.
authors.forename: Lee-Way
authors.initials: LW
authors.lastname: Jin
authors.affiliation: Department of Neurology, Emory University, Atlanta, GA, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Levey
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000378:metabolism*; D008297:Male; D008840:Microfilament Proteins; D017628:Microglia / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
chemical_list: C112986:AIF1 protein, human; D016229:Amyloid beta-Peptides; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D051664:Kv1.3 Potassium Channel; D008840:Microfilament Proteins; C498585:TUBB3 protein, human; D014404:Tubulin
keywords: Alzheimer's disease; Kv1.3; microglia; neuroinflammation; potassium channel