Focal white matter lesions drive grey matter inflammation and synapse loss - Nature

"Focal white matter lesions accumulate with age in the central nervous system and, in neurodegenerative conditions, their number correlates with cognitive and physical impairment. Multiple sclerosis is a demyelinating disorder characterized by white matter demyelinating lesions, while grey matter microgliosis and synaptic loss lead to irreversible neurodegeneration, thought to be the dominant mechanism underlying disability progression."

"Neurodegeneration in MS is characterized by low-grade inflammation and ineffective myelin regeneration. This is common in other neurodegenerative conditions, such as dementia and Alzheimer's disease, where white matter lesions occur early but have been traditionally considered secondary to neuronal loss."

"Changes in neuronal activity, microglial activation in the grey matter, and synapse engulfment occur in models of diffuse demyelination. The observed grey matter changes are often considered independent of the demyelinating injury, despite total brain volume loss and cognitive decline correlating with white matter lesion burden."

Focal white matter lesions accumulate with age in the CNS and correlate with cognitive and physical impairment in neurodegenerative conditions. Multiple sclerosis is characterized by these lesions, along with grey matter microgliosis and neuronal loss, leading to irreversible neurodegeneration. Low-grade inflammation and ineffective myelin regeneration are common in MS and other neurodegenerative disorders. Recent evidence suggests dysfunctional myelin may impact microglial and neuronal function. Despite the burden of these disorders, effective treatments to prevent progression are lacking, and the relationship between white matter lesions and neuronal function remains unclear.

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