PK11195 Labels Activated Microglia in Alzheimer's Disease and in Vivo in a Mouse Model Using PET

Overview

Journal Neurobiol Aging

Publisher Elsevier

Specialties Geriatrics
Neurology
Physiology

Date 2008 Jan 8

PMID 18178291

Citations 64

Authors

Sriram Venneti

Brian J Lopresti

Guoji Wang

Ronald L Hamilton

Chester A Mathis

William E Klunk

Udayan M Apte

Clayton A Wiley

Affiliations

Soon will be listed here.

Abstract

Activated microglia may promote neurodegeneration in Alzheimer's disease (AD) and may also help in amyloid clearance in immunization therapies. In vivo imaging of activated microglia using positron emission tomography (PET) could assist in defining the role of activated microglia during AD progression and therapeutics. We hypothesized that PK11195, a ligand that binds activated microglia, could label these cells in postmortem AD tissues and in vivo in an animal model of AD using PET. [(3)H](R)-PK11195 binding was significantly higher in AD frontal cortex compared to controls and correlated mainly with the abundance of immunohistochemically labeled activated microglia. With age, the brains of APP/PS1 transgenic mice showed progressive increase in [(3)H](R)-PK11195 binding and [(11)C](R)-PK11195 retention in vivo assessed using microPET, which correlated with the histopathological abundance of activated microglia. These results suggest that PK11195 binding in AD postmortem tissue and transgenic mice in vivo correlates with the extent of microglial activation and may help define the role of activated microglia in the pathogenesis and treatment of AD.

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