Cortical CD200-CD200R and CD47-SIRPα expression is associated with multiple sclerosis pathology.

Control of microglia activity through CD200-CD200R and CD47-SIRPα interactions has been implicated in brain homeostasis. Here, we assessed CD200, CD47, CD200R and SIRPα expression with qPCR and immunohistochemistry in multiple sclerosis (MS) normal-appearing cortical grey matter (NAGM), normal-appearing white matter (NAWM), cortical grey matter (GM) lesions and perilesional GM, and compared this to control GM and white matter (WM), to investigate possible altered control of microglia in MS. In MS NAGM, CD200 expression is lower compared with control GM, specifically in cortical layers 1 and 2, and CD200 expression in NAGM negatively correlates with the cortical lesion rate.

Disentangling the heterogeneity of multiple sclerosis through identification of independent neuropathological dimensions.

Multiple sclerosis (MS) is a heterogeneous neurological disorder with regards to clinical presentation and pathophysiology. Here, we investigated the heterogeneity of MS by performing an exploratory factor analysis on quantitative and qualitative neuropathology data collected for 226 MS donors in the Netherlands Brain Bank autopsy cohort. Three promising dimensions were identified and subsequently validated with clinical, neuropathological, and genetic data.

Profiling of microglia nodules in multiple sclerosis reveals propensity for lesion formation.

Microglia nodules (HLA-DR cell clusters) are associated with brain pathology. In this post-mortem study, we investigated whether they represent the first stage of multiple sclerosis (MS) lesion formation. We show that microglia nodules are associated with more severe MS pathology.

Ultrastructural Axon-Myelin Unit Alterations in Multiple Sclerosis Correlate with Inflammation.

Objective: Changes in the normal-appearing white matter (NAWM) in multiple sclerosis (MS) may contribute to disease progression. Here, we systematically quantified ultrastructural and subcellular characteristics of the axon-myelin unit in MS NAWM and determined how this correlates with low-grade inflammation.

Methods: Human brain tissue obtained with short postmortem delay and fixation at autopsy enables systematic quantification of ultrastructural characteristics.

White matter lesions in multiple sclerosis are enriched for CD20 CD8 tissue-resident memory T cells.

Brain CD8 CD69 tissue-resident memory T (T ) cells comprise a CD20 subset, which is proportionally larger in CD103-negative T cells. In multiple sclerosis (MS) lesions, CD20 T -cell proportions are increased. CD20-expression is associated with higher levels of CXCR6, Ki-67, and granzyme B, supporting CD20 T cells as a relevant subset in MS.