The role of amyloid-ß in white matter damage: possible common pathogenetic mechanisms in neurodegenerative and demyelinating diseases

Just as multiple sclerosis (MS) has long been primarily considered a white matter (WM) disease, Alzheimer's disease (AD) has for decades been regarded only as a grey matter disorder. However, convergent evidences have suggested that WM abnormalities are also important components of AD, at the same extent as axonal and neuronal loss is critically involved in MS pathophysiology since early clinical stages. These observations have motivated a more thorough investigation about the possible mechanisms that could link neuroinflammation and neurodegeneration, focusing on amyloid-ß (Aß). Neuroimaging studies have found that patients with AD have widespread WM abnormalities already at the earliest disease stages and prior to the presence of Aß plaques. Moreover, a correlation between cerebrospinal fluid (CSF) Aß levels and WM lesion load was found. On the other hand, recent studies suggest a predictive role for CSF Aß levels in MS, possibly due in the first instance to the reduced capacity for remyelination, consequently to a higher risk of WM damage progression, and ultimately to neuronal loss. We undertook a review of the recent findings concerning the involvement of CSF Aß levels in the MS disease course and of the latest evidence of AD related WM abnormalities, with the aim to discuss the potential causes that may connect WM damage and amyloid pathology.