Background Synaptic loss is an important factor in Alzheimer disease (AD); however, blood assays that conveniently and rapidly reflect changes in synaptic density are lacking. Purpose To correlate multiple potential synaptic blood markers with synaptic density measured using 18F-SynVesT-1, a fluorine 18 (18F)-labeled radiotracer, brain PET and to explore the independent associations between these markers and synaptic density. Materials and Methods This prospective study included 50 cognitively unimpaired (mean age, 65.0 years ± 8.3 [SD]; 37 female) participants and 70 participants with cognitive impairment (mean age, 69.5 years ± 7.9; 43 female) from the Memory Clinic of Shanghai Jiao Tong University Affiliated Ruijin Hospital and communities in Shanghai. Amyloid-β (Aβ) and tau were assessed using 18F-florbetapir and 18F-MK6240 PET/CT. Synaptic density was evaluated with 18F-SynVesT-1 PET/MRI. Pearson correlation analysis was used to investigate relationships of plasma (Aβ42/40 ratio, phosphorylated tau 181 [p-tau-181], glial fibrillary acid protein [GFAP], neurofilament light) and serum (C-reactive protein, tumor necrosis factor-α, α-synuclein, neurogranin, active plasminogen activator inhibitor-1, tissue plasminogen activator) biomarkers with synaptic density. Linear regression models and mediation analysis were used to explore effects of other AD-related pathologies on these relationships. Results Correlations were observed between increased p-tau-181 and GFAP and decreased synaptic density in global cortex (rp-tau-181 = -0.352, rGFAP = -0.386; both P < .001) and hippocampus (rp-tau-181 = -0.361, rGFAP = -0.369; both P < .001) at 18F-SynVesT-1 PET/MRI. The relationships between p-tau-181 and GFAP with 18F-SynVesT-1 PET/MRI persisted after controlling for plasma Aβ42/40 ratio, Aβ PET, or cortical thickness (P value range, <.001-.01). This association disappeared after controlling for tau PET (P value range, .08-.83). Conclusion Plasma p-tau-181 and GFAP are closely associated with synaptic density measured using 18F-SynVesT-1 PET/MRI, with the relationship primarily influenced by tau accumulation rather than Aβ deposition or cortical thickness. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Giannakopoulos in this issue.

中文翻译：

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血浆胶质纤维酸蛋白和磷酸化 tau 181 与 18F-SynVesT-1 脑 PET 成像突触前密度依赖性 tau 病理学的关联。


背景突触丢失是阿尔茨海默病 （AD） 的一个重要因素;然而，缺乏方便快速反映突触密度变化的血液检测。目的 将多种潜在的突触血标志物与使用 18F-SynVesT-1（一种氟 18 （18F） 标记的放射性示踪剂、脑 PET 测量的突触密度相关联，并探讨这些标志物与突触密度之间的独立关联。材料和方法 这项前瞻性研究包括 50 名认知无障碍参与者 （平均年龄，65.0 岁 ± 8.3 [SD];37 名女性） 和 70 名认知障碍参与者 （平均年龄，69.5 岁± 7.9 岁;43 名女性） 来自上海交通大学附属瑞金医院记忆诊所和社区。使用 18F-florbetapir 和 18F-MK6240 PET/CT 评估 β 淀粉样蛋白 （Aβ） 和 tau。用 18F-SynVesT-1 PET/MRI 评估突触密度。采用 Pearson 相关性分析研究血浆 （Aβ42/40 比值、磷酸化 tau 181 [p-tau-181]、神经胶质纤维酸蛋白 [GFAP]、神经丝光）和血清 （C 反应蛋白、肿瘤坏死因子-α、α-突触核蛋白、神经颗粒蛋白、活性纤溶酶原激活物抑制剂-1、组织纤溶酶原激活物）生物标志物与突触密度的关系。线性回归模型和中介分析用于探讨其他 AD 相关病理对这些关系的影响。结果 在 18F-SynVesT-1 PET/MRI 中观察到整体皮层 （rp-tau-181 = -0.352，rGFAP = -0.386;两者均 P < .001） 和海马 （rp-tau-181 = -0.361，rGFAP = -0.369;均 P < .001） p-tau-181 和 GFAP 增加与突触密度降低之间存在相关性。 在控制血浆 Aβ42/40 比值、 Aβ PET 或皮质厚度后，p-tau-181 与 GFAP 与 18F-SynVesT-1 PET/MRI 之间的关系仍然存在 （P 值范围，<.001-.01）。控制 tau PET 后，这种关联消失 （P 值范围，.08-.83）。结论 血浆 p-tau-181 和 GFAP 与 18F-SynVesT-1 PET/MRI 测量的突触密度密切相关，其关系主要受 tau 积累的影响，而不是 Aβ 沉积或皮质厚度。© RSNA，2024 年本文提供补充材料。另请参见本期 Giannakopoulos 的社论。