Journal
BRAIN
Volume 139, Issue -, Pages 39-46Publisher
OXFORD UNIV PRESS
DOI: 10.1093/brain/awv353
Keywords
neuropathology; multiple sclerosis; demyelination; synaptopathy; dendritic spines; cortical projection neurons
Categories
Funding
- Deutsche Forschungsgemeinschaft (DFG)
- Munich Center for Systems Neurology [EXC1010]
- Deutsche Forschungsgemeinschaft (DFG
- Munich Center for Systems Neurology) [EXC1010, Transregio 128, 1710]
- German Federal Ministry of Research and Education (BMBF
- Competence Network Multiple Sclerosis)
- European Research Council under the European Union's Seventh Framework Program (FP)
- ERC Grant [310932]
- 'Verein Therapieforschung fur multiple sclerosis-Kranke e.V.'
- Swiss National Science Foundation [PP00P3_152928]
- Klaus-Tschira Foundation
- Swiss multiple sclerosis society
- Gebert-Ruf Foundation
- Gemeinnutzige Hertie Stiftung
- Deutsche Forschungsgemeinschaft [Transregio SFB43]
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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.
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