Related Experiment Video
Updated: Jun 7, 2025
Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451
Published on: April 18, 2025
Plasma Glial Fibrillary Acid Protein and Phosphorated Tau 181 Association with Presynaptic Density-Dependent Tau
Junhao Wu1, Binyin Li1, Jie Wang1
1From the Department of Nuclear Medicine and PET Center, Huashan Hospital, Fudan University, Shanghai, China (J. Wu, J. Wang, Q.H., K.H., Y.G., F.X.); Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (B.L.); Department of Nuclear Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (X.C., Z.Y., J.Z.); Department of Gerontology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China (Q.G.); PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Conn (S.L., Y.H.H.); Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, China (T.G.); Center for Applied Statistics, Institute of Statistics and Big Data, Renmin University of China, Beijing, China (W.D.); and Shanghai Conlight Medical Laboratory, Shanghai, China (W.X., W.C., D.Y.).
Abstract:
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.
