title: Reconstruction of single cortical projection neurons reveals primary spine loss in multiple sclerosis.
abstract: Grey matter pathology has emerged as an important contributor to long-term disability in multiple sclerosis. To better understand where and how neuronal damage in the grey matter is initiated, we used high resolution confocal microscopy of Golgi-Cox impregnated tissue sections and reconstructed single cortical projection neurons in autopsies from eight patients with long-standing relapsing-remitting or secondary progressive multiple sclerosis and eight control patients without neurological disease. Analysis of several hundred individual neurons located in the insular, frontotemporal and occipital lobe revealed a widespread and pronounced loss of dendritic spines in multiple sclerosis cortex that occurs independent of cortical demyelination and axon loss. The presence of a primary synaptic pathology in the normal-appearing cortex of multiple sclerosis patients challenges current disease concepts and has important implications for our understanding of disease progression.
authors.affiliation: 1 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland doron.merkler@unige.ch martin.kerschensteiner@med.uni-muenchen.de.
authors.forename: Tanja
authors.initials: T
authors.lastname: Jürgens
authors.affiliation: 2 Institute of Clinical Neuroimmunology, Ludwig-Maximilians University Munich, Munich, Germany 3 Biomedical Center (BMC), Ludwig-Maximilians University Munich, Munich, Germany doron.merkler@unige.ch martin.kerschensteiner@med.uni-muenchen.de.
authors.forename: Mehrnoosh
authors.initials: M
authors.lastname: Jafari
authors.affiliation: 1 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
authors.forename: Mario
authors.initials: M
authors.lastname: Kreutzfeldt
authors.affiliation: 4 Department of Neuropathology, University Medical Centre, Göttingen, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Bahn
authors.affiliation: 4 Department of Neuropathology, University Medical Centre, Göttingen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.affiliation: 2 Institute of Clinical Neuroimmunology, Ludwig-Maximilians University Munich, Munich, Germany 3 Biomedical Center (BMC), Ludwig-Maximilians University Munich, Munich, Germany 5 Munich Cluster of Systems Neurology (SyNergy), Munich, Germany doron.merkler@unige.ch martin.kerschensteiner@med.uni-muenchen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Kerschensteiner
authors.affiliation: 1 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland 4 Department of Neuropathology, University Medical Centre, Göttingen, Germany 6 Division of Clinical Pathology, Geneva University Hospital, Geneva, Switzerland doron.merkler@unige.ch martin.kerschensteiner@med.uni-muenchen.de.
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
mesh_terms: D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology*; D049229:Dendritic Spines / Q000473:pathology*; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009474:Neurons / Q000473:pathology*
keywords: cortical projection neurons; demyelination; dendritic spines; multiple sclerosis; neuropathology; synaptopathy