CSF synaptic biomarkers and cognitive impairment in multiple sclerosis

Area of Science:

• Neuroscience
• Biomarker Discovery
• Neurology

Background:

• Multiple sclerosis (MS) is associated with cognitive impairment (CI), potentially due to synaptic dysfunction.
• Cerebrospinal fluid (CSF) biomarkers of synaptic function remain largely unexplored in MS.

Purpose of the Study:

• To investigate CSF levels of synaptosomal-associated protein 25 (SNAP-25), β-synuclein, and neurogranin in early relapsing MS patients.
• To determine the association of these synaptic biomarkers with cognitive function, disease duration, brain volume, and neurofilament light chain protein (NfL).

Main Methods:

• CSF samples were analyzed for SNAP-25, β-synuclein, and neurogranin in 48 untreated MS patients and 50 controls with other neurological diseases (ONDs).
• Associations with neuropsychological tests, MRI data, and CSF NfL levels were examined.

Main Results:

• CSF synaptic protein levels did not significantly differ between MS patients and ONDs, except for a slight increase in SNAP-25 in MS.
• CSF synaptic markers correlated positively with each other and with CSF NfL.
• Lower levels of CSF SNAP-25, β-synuclein, and neurogranin were observed in MS patients with cognitive impairment compared to those without.
• Biomarker levels correlated with longer disease duration and reduced brain volumes, particularly in the thalamus.

Conclusions:

• Reduced CSF synaptic biomarker levels are associated with longer disease duration and lower brain volumes in MS patients.
• These CSF synaptic biomarkers may serve as indicators for identifying MS patients at risk of cognitive impairment.