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

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This study shows reduced synaptic density in people with multiple sclerosis (MS) using [11C]UCB-J-PET imaging. Synaptic loss in gray matter is linked to cognitive impairment in MS patients.

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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 (VT).
  • 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 (VT = 15.65 mL/cm3) compared to HCs (VT = 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.