Neuropathological Evidence of Reduced Amyloid Beta and Neurofibrillary Tangles in Multiple Sclerosis Cortex

Abstract Multiple sclerosis (MS) and Alzheimer’s disease (AD) are neurodegenerative diseases demonstrating age-related accumulation of disability. Inflammation lasting decades is a paradigmatic feature of MS pathology that variably relates to neurodegeneration, while the accumulation of Aβ plaques and neurofibrillary tangles (NFT) are cornerstones of AD pathology. However, few studies investigated the accumulation of amyloids in MS. We investigated Aβ deposition and NFT density in temporal or frontal cortices derived from a large post-mortem cohort of MS (n=78) and age and sex-matched control (n=65) cases. We found reduced Aβ burden in MS cases compared with controls, particularly in cases below 65-years-of-age. NFT were similarly reduced in MS compared to controls, notably in cases above 65 years-of-age. Higher Aβ deposition predicted greater NFT density in MS. These findings suggest that MS-related factors may influence Aβ and NFT deposition and/or clearance. This work highlights new therapeutic perspectives relevant for both MS and AD.