We investigated the Aβ burden in post-mortem samples of temporal or frontal cortex in MS and evaluate its relationships with motor cortical pathology.

Multiple sclerosis (MS) and Alzheimer’s disease (AD) represent major foci of interest for neuropathological research. MS is the quintessential neuroinflammatory disease, but inflammation is increasingly recognised as an independent driver of AD pathology, with microglial activation thought to play a key role. One might expect amyloid deposition in the MS brain given that the pathological hallmarks of amyloid plaques and neurofibrillary tangles seen in AD are also seen to a lesser extent in the normal aging brain. Moreover, coexistence of MS and AD pathology is likely since there is anatomical overlap in the cortical areas affected. The chronic inflammatory milieu of the MS cortex thus provides a unique model in which to further investigate the role that inflammation plays in amyloid physiology.

An autopsy cohort of pathologically confirmed MS (n=78) and control (n=67) cases was used, where Aβ burden was related to neuronal and microglial/macrophages densities. Quantitative and semi-quantitative analyses were performed and related to pathological features.

We found reduced Aβ burden in normal-appearing grey matter of MS cases that died below median age (64 years-old) compared with matched controls, with further reduction noted in MS-specific subpial demyelinated lesions. An increase in CD68+ microglial/macrophage expression and neuronal survival related to the reduction in Aβ was found in MS cases that died below median age.

These findings suggest that MS-related factors, including microglia/macrophage inflammation, influence Aβ deposition and neurodegeneration thereby highlighting new therapeutic perspectives relevant for both MS and AD.