Reconstruction of single cortical projection neurons reveals primary spine loss in multiple sclerosis

Brain. 2016 Jan;139(Pt 1):39-46. doi: 10.1093/brain/awv353. Epub 2015 Dec 14.


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.

Keywords: cortical projection neurons; demyelination; dendritic spines; multiple sclerosis; neuropathology; synaptopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cerebral Cortex / pathology*
  • Dendritic Spines / pathology*
  • Female
  • Gray Matter / pathology
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / pathology*
  • Neurons / pathology*