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01-09-2016 | Original Paper

Peripheral monocytes are functionally altered and invade the CNS in ALS patients

Authors: Lisa Zondler, Kathrin Müller, Samira Khalaji, Corinna Bliederhäuser, Wolfgang P. Ruf, Veselin Grozdanov, Meinolf Thiemann, Katrin Fundel-Clemes, Axel Freischmidt, Karlheinz Holzmann, Benjamin Strobel, Patrick Weydt, Anke Witting, Dietmar R. Thal, Anika M. Helferich, Bastian Hengerer, Kay-Eberhard Gottschalk, Oliver Hill, Michael Kluge, Albert C. Ludolph, Karin M. Danzer, Jochen H. Weishaupt

Published in: Acta Neuropathologica | Issue 3/2016

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease affecting primarily the upper and lower motor neurons. A common feature of all ALS cases is a well-characterized neuroinflammatory reaction within the central nervous system (CNS). However, much less is known about the role of the peripheral immune system and its interplay with CNS resident immune cells in motor neuron degeneration. Here, we characterized peripheral monocytes in both temporal and spatial dimensions of ALS pathogenesis. We found the circulating monocytes to be deregulated in ALS regarding subtype constitution, function and gene expression. Moreover, we show that CNS infiltration of peripheral monocytes correlates with improved motor neuron survival in a genetic ALS mouse model. Furthermore, application of human immunoglobulins or fusion proteins containing only the human Fc, but not the Fab antibody fragment, increased CNS invasion of peripheral monocytes and delayed the disease onset. Our results underline the importance of peripheral monocytes in ALS pathogenesis and are in agreement with a protective role of monocytes in the early phase of the disease. The possibility to boost this beneficial function of peripheral monocytes by application of human immunoglobulins should be evaluated in clinical trials.

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Title: Peripheral monocytes are functionally altered and invade the CNS in ALS patients
Authors: Lisa Zondler
Kathrin Müller
Samira Khalaji
Corinna Bliederhäuser
Wolfgang P. Ruf
Veselin Grozdanov
Meinolf Thiemann
Katrin Fundel-Clemes
Axel Freischmidt
Karlheinz Holzmann
Benjamin Strobel
Patrick Weydt
Anke Witting
Dietmar R. Thal
Anika M. Helferich
Bastian Hengerer
Kay-Eberhard Gottschalk
Oliver Hill
Michael Kluge
Albert C. Ludolph
Karin M. Danzer
Jochen H. Weishaupt
Publication date: 01-09-2016
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 3/2016
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-016-1548-y

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Peripheral monocytes are functionally altered and invade the CNS in ALS patients

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