Role of amyloid-β CSF levels in cognitive deficit in MS

•Amyloid-β (Aβ) causes cognitive defects, by inhibiting long-term potentiation (LTP).•LTP can be measured in humans by transcranial magnetic stimulation (TMS).•In multiple sclerosis (MS) patients brain plasticity is altered.•Aβ is reduced in MS cerebrospinal fluid (CSF) and correlates with MS cognitive defects.•Aβ CSF levels correlate with TMS measure of synaptic plasticity in MS.

Multiple sclerosis (MS) is the most common neurological disease of the young adults. Although being long considered as a pure white matter (WM) disease, growing evidence indicates that in MS the gray matter (GM) is affected as well, and that GM pathology correlates with cognitive function deterioration in MS. Indeed, MS is increasingly recognized to cause cognitive deficits since its early stages. Therefore, the identification of a biomarker with good diagnostic and prognostic power is of great importance for monitoring and preventing cognitive impairment in MS patients. A possibility arises from the combination of two different measures of neuronal injury: the levels of amyloid-β1 -42 in cerebrospinal fluid (CSF), which have been found associated with cognitive decline in Alzheimer disease (AD); the brain synaptic plasticity, which is a measure of cognitive reserve and can be explored safely in humans by means of transcranial magnetic stimulation.In this review, we discuss the relevance of amyloid-β1 -42 in MS disease and its link to long-term potentiation (LTP), which is the most studied form of synaptic plasticity, providing evidence for their combined use in cognitive assessment in MS patients.