[en] In Alzheimer's disease (AD), persistent microglial activation as sign of chronic neuroinflammation contributes to disease progression. Our study aimed to in vivo visualize and quantify microglial activation in 13- to 15-month-old AD mice using [(11)C]-(R)-PK11195 and positron emission tomography (PET). We attempted to modulate neuroinflammation by subjecting the animals to an anti-inflammatory treatment with pioglitazone (5-weeks' treatment, 5-week wash-out period). [(11)C]-(R)-PK11195 distribution volume values in AD mice were significantly higher compared with control mice after the wash-out period at 15 months, which was supported by immunohistochemistry data. However, [(11)C]-(R)-PK11195 μPET could not demonstrate genotype- or treatment-dependent differences in the 13- to 14-month-old animals, suggesting that microglial activation in AD mice at this age and disease stage is too mild to be detected by this imaging method.
Disciplines :
Neurology
Author, co-author :
Rapic, Sara; European Institute for Molecular Imaging, Westfalian Wilhelms-University Münster, Münster, Germany
Backes, Heiko; Max Planck Institute for Neurological Research, Cologne, Germany
Viel, Thomas; European Institute for Molecular Imaging (EIMI), Westfalian Wilhelms-University (WWU) Münster, Münster, Germany ; Max Planck Institute for Neurological Research, Cologne, Germany
Kummer, Markus P; Department of Neurology Clinical Neurosciences, University of Bonn, Bonn, Germany
Monfared, Parisa; European Institute for Molecular Imaging (EIMI), Westfalian Wilhelms-University (WWU) Münster, Münster, Germany ; Max Planck Institute for Neurological Research, Cologne, Germany
Neumaier, Bernd; Max Planck Institute for Neurological Research, Cologne, Germany
Vollmar, Stefan; Max Planck Institute for Neurological Research, Cologne, Germany
Hoehn, Mathias; Max Planck Institute for Neurological Research, Cologne, Germany
Van der Linden, Annemie; Bio-Imaging Lab., University of Antwerp, Antwerp, Belgium
HENEKA, Michael ; Department of Neurology Clinical Neurosciences, University of Bonn, Bonn, Germany
Jacobs, Andreas H; European Institute for Molecular Imaging (EIMI), Westfalian Wilhelms-University (WWU) Münster, Münster, Germany ; Interdisciplinary Centre for Clinical Research (IZKF), WWU Münster, Münster, Germany ; Department of Nuclear Medicine, WWU Münster, Münster, Germany
External co-authors :
yes
Language :
English
Title :
Imaging microglial activation and glucose consumption in a mouse model of Alzheimer's disease.
This work was supported in part by 6th FW DiMI-NoE LSHB-CT-2005-512146, IZKF-SchwJ3/001/11, and 7th FW INMiND GA N°278850. The studies were performed as part of the master thesis of S.R. during the European Master of Molecular Imaging (EMMI). We thank Drs Sascha Weggen and Claus Pietrzik for providing the antibody IC16.
Kummer M.P., Heneka M.T. PPARs in Alzheimer's disease. PPAR Res 2008, 403896.
Perry V.H., Nicoll J.A., Holmes C. Microglia in neurodegenerative disease. Nat. Rev. Neurol 2010, 6:193-201.
Venneti S., Lopresti B.J., Wang G., Hamilton R.L., Mathis C.A., Klunk W.E., Apte U.M., Wiley C.A. PK11195 labels activated microglia in Alzheimer's disease and in vivo in a mouse model using PET. Neurobiol. Aging 2009, 30:1217-1226.
