Demyelination with preferential MAG loss: A complex message from MS paraffin blocks

Multiple sclerosis (MS) is generally considered to be a demyelinating autoimmune disorder. However, neuropathological examinations of MS lesions do not support this concept. Demyelination with preferential loss of myelin-associated glycoprotein (MAG) is a common finding in MS tissues and has been reported by several groups. As MAG is located in ad-axonal myelin layers and is not accessible to infiltrating immune cells, demyelination with preferred loss of MAG may be suggestive of a primary oligodendrocytopathy in MS. Moreover, it has been shown that oligodendrocytopathy may precede the infiltration of inflammatory cells at the lesion site. In this paper, we review studies of neuropathology of MS tissues that reported this type of demyelination and then we discuss three emerging explanations that are trying to interpret this mismatched observation.