Synaptic Density in Multiple Sclerosis: An In Vivo Study Using [¹¹C]UCB-J-PET Imaging

Area of Science:

• Neuroscience
• Radiology

Background:

• Multiple sclerosis (MS) is a chronic CNS disease involving inflammation and neurodegeneration affecting white and gray matter.
• Synaptic loss, a key pathological feature, remains understudied in people with MS (pwMS).

Purpose of the Study:

• To investigate in vivo synaptic loss in pwMS using [11C]UCB-J-PET imaging.
• To quantify synaptic vesicle glycoprotein 2A (SV2A) availability.
• To explore associations between synaptic loss and clinical/cognitive measures in pwMS.

Main Methods:

• Ten pwMS and 8 healthy controls (HCs) underwent high-resolution [11C]UCB-J-PET imaging and MRI.
• SV2A availability was measured as distribution volume (V_T).
• Associations with Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT) were analyzed, considering prior clinical/cognitive data.

Main Results:

• PwMS exhibited significantly lower SV2A availability in cortical gray matter (V_T = 15.65 mL/cm³) compared to HCs (V_T = 18.14 mL/cm³; p=0.029).
• Reduced SV2A availability in cortical gray matter correlated with lower SDMT scores in pwMS (r=0.071, p=0.021).
• No association was found between physical disability (EDSS) and SV2A availability.

Conclusions:

• In vivo [11C]UCB-J PET imaging provides evidence of reduced synaptic density in pwMS.
• Synaptic loss is linked to cognitive impairment in MS.
• [11C]UCB-J PET imaging shows potential for assessing gray matter pathology in MS.