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

Multiple sclerosis (MS) and Alzheimer's disease are neurodegenerative diseases with age-related disability accumulation. In MS, inflammation spans decades, whereas AD is characterized by Aβ plaques and neurofibrillary tangles (NFT). Few studies explore accumulation of amyloids in MS. We examined Aβ deposition and NFT density in temporal and frontal cortices from postmortem MS (n = 75) and control (n = 66) cases. Compared with controls, MS cases showed reduced Aβ, especially in those aged <65 years, and reduced NFT, notably in cases aged >65 years. Aβ deposition predicted greater NFT density both in MS cases and controls. MS-related factors may affect Aβ/NFT deposition and/or clearance, offering new therapeutic insights for both diseases. ANN NEUROL 2025;97:1067-1073.