Widespread synaptic loss in multiple sclerosis.

Abstract

This scientific commentary refers to ‘Reconstruction of single cortical projection neurons reveals primary spine loss in multiple sclerosis’, by Jurgens et al. (doi:10.1093/brain/awv353). It has been estimated that the human brain comprises 8.6 × 1011 neurons that are connected by ∼1014 synapses (Pakkenberg et al. , 2003). These synapses decline in number during ageing and show accelerated loss in neurodegenerative diseases such as Alzheimer’s disease (Selkoe, 2002). However, whether synaptic loss also occurs in multiple sclerosis and, if so, how it relates to demyelination and axonal input, is unclear. In this issue of Brain , Jurgens et al. use elegant staining and imaging techniques to shed light on synaptic pathology in multiple sclerosis, and conclude that such pathology is widespread and occurs without coincident demyelination or axonal degeneration (Jurgens et al. , 2016). While multiple sclerosis was initially considered to be a chronic inflammatory disease that mainly affects white matter, it is now clear that grey matter pathology such as neuronal and axonal loss is equally widespread (Friese et al. , 2014). Demyelinated areas in the hippocampi of multiple sclerosis brains show a consistent reduction in synaptic density (Dutta et al. , 2011). Grey matter demyelination and accompanying neuronal demise contribute to permanent neurological disability in multiple sclerosis as revealed by their correlation with disease progression (Calabrese et al. , 2013). Similarly, cognitive dysfunction is found in over 50% of patients with multiple sclerosis and can be attributed to grey matter pathology (Chiaravalloti and DeLuca, 2008). While all neuronal subcellular structures are affected …