Pharmacopsychiatry 2015; 25 - A82
DOI: 10.1055/s-0035-1558020

CCL17-deficiency alters myeloid cell-responses and prevents cognitive decline in APP/PS1-mice

K Neitzert 1, Ö Albayram 1, O Ambrée 2, R Lundt 1, I Karaca 3, M Cron 1, C Müller 1, I Förster 4, A Bilkei 1, A Gorzo 5, F Jessen 3, J Walter 6, S Scheu 7, W Maier 1, A Zimmer 2, J Alferink 1
  • 1Institute of Molecular Psychiatry, University of Bonn, Germany
  • 2Department of Psychiatry, University of Münster, Germany
  • 3Laboratory of Molecular Cell Biology, Department of Neurology, University of Bonn, Germany
  • 4Immunology and Environment, Life & Medical Sciences Institute (LIMES), University of Bonn, Germany
  • 5Department of Psychiatry, University of Köln, Germany
  • 6Institute of Medical Microbiology and Hospital Hygiene, University of Duesseldorf
  • 7Department of Psychiatry, University of Bonn, Germany

The CC-chemokine CCL17 regulates leukocyte trafficking during inflammation, however, its role in Alzheimerʼs disease (AD) pathogenesis remains undefined. Here we show that CCL17 is enhanced in AD patients when compared to healthy controls. In a mouse model for AD we found that CCL17 controls amyloid β (Aβ) deposition, neuroinflammation, and cognitive decline. CCL17 deficient APP/PS1 mice (APP/PS1-CCL17E/E) showed reduced Aβ brain levels, and were protected against neuronal loss and cognitive deficits. Enhanced microgliosis and brain recruitment of Ly6C+CCR2+ macrophages expressing mannose receptors associated with elevated brain IL-10 levels pointed to beneficial immune responses in these mice. In the absence of CCL17 we observed accelerated uptake of Aβ, enhanced IL-10 release by activated microglia and upregulated Aβ-degrading enzyme neprilysin (NEP) in APP/PS1 brains. These newly identified roles for CCL17 in regulating microglia function and memory loss suggest that targeting this chemokine may harbor therapeutic potential for the treatment of AD.

This study was supported by Alzheimer Forschung Initiative (AFI)