Potassium channel Kv1.3 is highly expressed by microglia in human Alzheimer's disease

Srikant Rangaraju, Marla Gearing, Lee-Way Jin, Allan Levey

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)797-808
Number of pages12
JournalJournal of Alzheimer's Disease
Volume44
Issue number3
DOIs
StatePublished - 2015

Fingerprint

Kv1.3 Potassium Channel
Microglia
Alzheimer Disease
Brain
Voltage-Gated Potassium Channels
Amyloid Plaques
Frontal Lobe
Autoimmunity
Amyloid
Innate Immunity
Astrocytes
Fluorescent Antibody Technique
Reactive Oxygen Species
Cell Count
Western Blotting
Staining and Labeling

Keywords

  • Alzheimer's disease
  • Kv1.3
  • microglia
  • neuroinflammation
  • potassium channel

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Cite this

Potassium channel Kv1.3 is highly expressed by microglia in human Alzheimer's disease. / Rangaraju, Srikant; Gearing, Marla; Jin, Lee-Way; Levey, Allan.

In: Journal of Alzheimer's Disease, Vol. 44, No. 3, 2015, p. 797-808.

Research output: Contribution to journalArticle

Rangaraju, Srikant ; Gearing, Marla ; Jin, Lee-Way ; Levey, Allan. / Potassium channel Kv1.3 is highly expressed by microglia in human Alzheimer's disease. In: Journal of Alzheimer's Disease. 2015 ; Vol. 44, No. 3. pp. 797-808.
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