Age-related changes in multiple sclerosis and experimental autoimmune encephalomyelitis

Area of Science:

• Neuroscience
• Immunology
• Pathology

Background:

• Multiple sclerosis (MS) involves neurodegeneration, but underlying mechanisms require further elucidation.
• Early-stage neurodegeneration in MS is often clinically silent, becoming apparent with age and leading to progressive disability.
• Effective therapies for MS progression necessitate a deeper understanding of its pathological drivers.

Purpose of the Study:

• To review pathological correlates of multiple sclerosis (MS) disease progression.
• To highlight novel mouse models that replicate key progressive MS changes.
• To offer new perspectives on therapeutic strategies for protecting against MS-associated neurodegeneration.

Main Methods:

• Review of existing literature on MS pathology and disease progression.
• Analysis of emerging preclinical mouse models of progressive MS.
• Synthesis of current knowledge to propose therapeutic avenues.

Main Results:

• Central nervous system (CNS)-intrinsic inflammation and leptomeningeal remodeling are proposed as early contributors to MS neurodegeneration.
• Ageing exacerbates clinically silent neurodegenerative changes, leading to manifest progressive disability in MS.
• Emerging mouse models offer valuable tools for studying MS progression.

Conclusions:

• Targeting CNS inflammation and leptomeningeal changes may offer therapeutic benefits in early MS.
• Understanding the interplay between ageing and neurodegeneration is crucial for managing progressive MS.
• Developing neuroprotective strategies is essential for preventing disability in multiple sclerosis.