Multiple sclerosis synaptic connectome: Insights from fluid biomarkers

Area of Science:

• Neuroscience
• Biomarkers
• Multiple Sclerosis Research

Background:

• Multiple sclerosis (MS) is a chronic central nervous system disease characterized by immune-mediated damage and neurodegeneration.
• Brain network disconnection, resulting from demyelination, axonal loss, and atrophy, is increasingly linked to MS progression and disability.
• Synaptic dysfunction is implicated in MS-related connectome changes, yet objective measures are lacking.

Purpose of the Study:

• To review the role of synaptic dysfunction and loss in MS.
• To explore synaptic proteins as potential fluid biomarkers for synaptic integrity in MS.
• To discuss current findings, challenges, and future directions for synaptic biomarker research in MS.

Main Methods:

• Literature review focusing on synaptic dysfunction in MS.
• Analysis of studies investigating synaptic proteins (presynaptic, postsynaptic, astrocyte-derived) as fluid biomarkers.
• Discussion of methodological challenges and future research needs.

Main Results:

• Synaptic proteins, including SNAP-25, VAMP-2, β-synuclein, neurogranin, and NPTX2, are measurable in cerebrospinal fluid and blood.
• These proteins reflect synaptic dysfunction and loss in MS, analogous to findings in other neurodegenerative diseases.
• Preliminary data suggest potential for these markers in assessing synaptic integrity.

Conclusions:

• Synaptic proteins represent a promising avenue for fluid biomarker development in MS.
• Further research is needed to validate these markers and understand their temporal dynamics and relationship with neuroinflammation and neurodegeneration.
• Objective measures of synaptic integrity could significantly advance MS diagnosis and management.