PK11195 labels activated microglia in Alzheimer's disease and in vivo in a mouse model using PET.
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.
Venneti
Sriram
S
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Lopresti
Brian J
BJ
Wang
Guoji
G
Hamilton
Ronald L
RL
Mathis
Chester A
CA
Klunk
William E
WE
Apte
Udayan M
UM
Wiley
Clayton A
CA
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000000981:diagnostic imaging / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging; D006801:Humans; D007546:Isoquinolines; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000000981:diagnostic imaging* / Q000502:physiology; D049268:Positron-Emission Tomography / Q000379:methods*; D053764:Presenilin-1 / Q000235:genetics; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000235:genetics; D014316:Tritium
C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D007546:Isoquinolines; D053764:Presenilin-1; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D014316:Tritium; C037850:PK 11195