Amelie Luoma, Markus Matilainen, Jouni Mikael Tuisku, Richard Aarnio, Taru Nikkilä, Sini Laaksonen, Mikko Koivumäki, Eveliina Honkonen, Marjo Nylund, Saara Wahlroos, Olof Solin, Ming-Kai Chen, Takuya Toyonaga, Jussi Lehto, Anniina Snellman, Juha O Rinne, Laura M Airas
{"title":"多发性硬化症突触密度的体内研究[11C]UCB-J-PET成像。","authors":"Amelie Luoma, Markus Matilainen, Jouni Mikael Tuisku, Richard Aarnio, Taru Nikkilä, Sini Laaksonen, Mikko Koivumäki, Eveliina Honkonen, Marjo Nylund, Saara Wahlroos, Olof Solin, Ming-Kai Chen, Takuya Toyonaga, Jussi Lehto, Anniina Snellman, Juha O Rinne, Laura M Airas","doi":"10.1212/NXI.0000000000200435","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>Multiple sclerosis (MS) is a chronic inflammatory disease coupled with neurodegenerative processes affecting both the white matter and gray matter (GM) in the CNS. Several histopathologic studies have reported a reduction in synaptic density in various areas of the brain. However, this pathologic feature is yet an unexplored entity among people with MS (pwMS). Therefore, we sought to investigate synaptic loss in vivo by quantifying the synaptic vesicle glycoprotein 2A using [<sup>11</sup>C]UCB-J-PET imaging and to explore associations with clinical and cognitive measures.</p><p><strong>Methods: </strong>Ten pwMS and 8 healthy controls (HCs) underwent high-resolution [<sup>11</sup>C]UCB-J-PET imaging and MRI. SV2A availability was determined using the tissue-to-plasma concentration ratio at equilibrium (distribution volume; V<sub>T</sub>). We furthermore explored associations between PET imaging results and clinical and cognitive measures in pwMS (assessed with the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test [SDMT]). In addition, we considered volumetric, clinical, and cognitive measures during a 5-year period before PET imaging.</p><p><strong>Results: </strong>Ten pwMS (7 women [70%], median [interquartile range] age, 53 [50-56]) years were compared with 8 HCs (6 women [75%]; age, 51 [50-70] years). PwMS had a significantly lower SV2A availability in the cortical GM (pwMS: mean [SD], V<sub>T</sub> = 15.65 mL/cm<sup>3</sup> [2.26]; HCs: V<sub>T</sub> = 18.14 mL/cm<sup>3</sup> [2.09]; <i>p =</i> 0.029, <i>t</i> test), as well as in several subcortical regions. Moreover, a lower SV2A availability in cortical GM correlated significantly with reduced SDMT values in pwMS (<i>r</i> = 0.071, <i>p</i> = 0.021; Spearman correlation coefficient). No association between physical disability (measured using EDSS) and SV2A availability was found.</p><p><strong>Discussion: </strong>Using in vivo [<sup>11</sup>C]UCB-J PET imaging, we provide evidence of reduced synaptic density in pwMS. Furthermore, the results reveal a link between synaptic loss and cognitive impairment. These findings highlight the potential of [<sup>11</sup>C]UCB-J PET imaging as a promising tool for assessing clinically relevant aspects of GM pathology in MS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 5","pages":"e200435"},"PeriodicalIF":7.8000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227148/pdf/","citationCount":"0","resultStr":"{\"title\":\"Synaptic Density in Multiple Sclerosis: An In Vivo Study Using [<sup>11</sup>C]UCB-J-PET Imaging.\",\"authors\":\"Amelie Luoma, Markus Matilainen, Jouni Mikael Tuisku, Richard Aarnio, Taru Nikkilä, Sini Laaksonen, Mikko Koivumäki, Eveliina Honkonen, Marjo Nylund, Saara Wahlroos, Olof Solin, Ming-Kai Chen, Takuya Toyonaga, Jussi Lehto, Anniina Snellman, Juha O Rinne, Laura M Airas\",\"doi\":\"10.1212/NXI.0000000000200435\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>Multiple sclerosis (MS) is a chronic inflammatory disease coupled with neurodegenerative processes affecting both the white matter and gray matter (GM) in the CNS. Several histopathologic studies have reported a reduction in synaptic density in various areas of the brain. However, this pathologic feature is yet an unexplored entity among people with MS (pwMS). Therefore, we sought to investigate synaptic loss in vivo by quantifying the synaptic vesicle glycoprotein 2A using [<sup>11</sup>C]UCB-J-PET imaging and to explore associations with clinical and cognitive measures.</p><p><strong>Methods: </strong>Ten pwMS and 8 healthy controls (HCs) underwent high-resolution [<sup>11</sup>C]UCB-J-PET imaging and MRI. SV2A availability was determined using the tissue-to-plasma concentration ratio at equilibrium (distribution volume; V<sub>T</sub>). We furthermore explored associations between PET imaging results and clinical and cognitive measures in pwMS (assessed with the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test [SDMT]). In addition, we considered volumetric, clinical, and cognitive measures during a 5-year period before PET imaging.</p><p><strong>Results: </strong>Ten pwMS (7 women [70%], median [interquartile range] age, 53 [50-56]) years were compared with 8 HCs (6 women [75%]; age, 51 [50-70] years). PwMS had a significantly lower SV2A availability in the cortical GM (pwMS: mean [SD], V<sub>T</sub> = 15.65 mL/cm<sup>3</sup> [2.26]; HCs: V<sub>T</sub> = 18.14 mL/cm<sup>3</sup> [2.09]; <i>p =</i> 0.029, <i>t</i> test), as well as in several subcortical regions. Moreover, a lower SV2A availability in cortical GM correlated significantly with reduced SDMT values in pwMS (<i>r</i> = 0.071, <i>p</i> = 0.021; Spearman correlation coefficient). No association between physical disability (measured using EDSS) and SV2A availability was found.</p><p><strong>Discussion: </strong>Using in vivo [<sup>11</sup>C]UCB-J PET imaging, we provide evidence of reduced synaptic density in pwMS. Furthermore, the results reveal a link between synaptic loss and cognitive impairment. These findings highlight the potential of [<sup>11</sup>C]UCB-J PET imaging as a promising tool for assessing clinically relevant aspects of GM pathology in MS.</p>\",\"PeriodicalId\":19472,\"journal\":{\"name\":\"Neurology® Neuroimmunology & Neuroinflammation\",\"volume\":\"12 5\",\"pages\":\"e200435\"},\"PeriodicalIF\":7.8000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227148/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurology® Neuroimmunology & Neuroinflammation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1212/NXI.0000000000200435\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurology® Neuroimmunology & Neuroinflammation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1212/NXI.0000000000200435","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/3 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Synaptic Density in Multiple Sclerosis: An In Vivo Study Using [11C]UCB-J-PET Imaging.
Background and objectives: Multiple sclerosis (MS) is a chronic inflammatory disease coupled with neurodegenerative processes affecting both the white matter and gray matter (GM) in the CNS. Several histopathologic studies have reported a reduction in synaptic density in various areas of the brain. However, this pathologic feature is yet an unexplored entity among people with MS (pwMS). Therefore, we sought to investigate synaptic loss in vivo by quantifying the synaptic vesicle glycoprotein 2A using [11C]UCB-J-PET imaging and to explore associations with clinical and cognitive measures.
Methods: Ten pwMS and 8 healthy controls (HCs) underwent high-resolution [11C]UCB-J-PET imaging and MRI. SV2A availability was determined using the tissue-to-plasma concentration ratio at equilibrium (distribution volume; VT). We furthermore explored associations between PET imaging results and clinical and cognitive measures in pwMS (assessed with the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test [SDMT]). In addition, we considered volumetric, clinical, and cognitive measures during a 5-year period before PET imaging.
Results: Ten pwMS (7 women [70%], median [interquartile range] age, 53 [50-56]) years were compared with 8 HCs (6 women [75%]; age, 51 [50-70] years). PwMS had a significantly lower SV2A availability in the cortical GM (pwMS: mean [SD], VT = 15.65 mL/cm3 [2.26]; HCs: VT = 18.14 mL/cm3 [2.09]; p = 0.029, t test), as well as in several subcortical regions. Moreover, a lower SV2A availability in cortical GM correlated significantly with reduced SDMT values in pwMS (r = 0.071, p = 0.021; Spearman correlation coefficient). No association between physical disability (measured using EDSS) and SV2A availability was found.
Discussion: Using in vivo [11C]UCB-J PET imaging, we provide evidence of reduced synaptic density in pwMS. Furthermore, the results reveal a link between synaptic loss and cognitive impairment. These findings highlight the potential of [11C]UCB-J PET imaging as a promising tool for assessing clinically relevant aspects of GM pathology in MS.
期刊介绍：
Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.
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