The associations between synaptic density and “A/T/N” biomarkers in Alzheimer’s disease: An 18 F-SynVesT-1 PET/MR study

• Published in: Journal of cerebral blood flow and metabolism Vol. 44; no. 7; pp. 1199 - 1207
• Main Authors: Li, Junpeng, Huang, Qi, Qi, Na, He, Kun, Li, Songye, Huang, Lin, Pan, Fengfeng, Ren, Shuhua, Hua, Fengchun, Huang, Yiyun, Guan, Yihui, Guo, Qihao, Zhao, Jun, Xie, Fang
• Format: Journal Article
• Language: English
• Published: United States 01.07.2024
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Amyloid beta-Peptides - metabolism; Biomarkers; Cognitive Dysfunction - diagnostic imaging; Cognitive Dysfunction - metabolism; Female; Fluorine Radioisotopes; Humans; Magnetic Resonance Imaging - methods; Male; Membrane Glycoproteins - metabolism; Middle Aged; Nerve Tissue Proteins - metabolism; Positron Emission Tomography Computed Tomography - methods; Positron-Emission Tomography - methods; Radiopharmaceuticals; Synapses - metabolism; Synapses - pathology; tau Proteins - metabolism; amyloid-β deposition; plasma biomarkers; Synaptic vesicle glycoprotein 2A; cognitive performance; glucose metabolism
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1177/0271678X241230733

A newly developed SV2A radiotracer, 18 F-SynVesT-1, was used in this study to investigate synaptic density and its association with Alzheimer’s disease (AD) “A/T/N” biomarkers. The study included a cohort of 97 subjects, consisting of 64 patients with cognitive impairment (CI) and 33 individuals with normal cognition (CU). All subjects underwent 18 F-SynVesT-1 PET/MR and 18 F-florbetapir PET/CT scans. Additionally, a subgroup of individuals also underwent 18 F-MK-6240, 18 F-FDG PET/CT, plasma Aβ42/Aβ40 and p-tau181 tests. The differences in synaptic density between the groups and the correlations between synaptic density and AD “A/T/N” biomarkers were analyzed. The results showed that compared to the CU group, the CI with Aβ+ (CI+) group exhibited the most pronounced synapse loss in the hippocampus, with some loss also observed in the neocortex. Furthermore, synaptic density in the hippocampus and parahippocampal gyrus showed associations with AD biomarkers detected by both imaging and plasma tests in the CI group. The associations between synaptic density and FDG uptake and hippocampal volume were also observed in the CI+ group. In conclusion, the study demonstrated significant synaptic density loss, as measured by the promising tracer 18 F-SynVesT-1, and its close correlation with “A/T/N” biomarkers in patients with both Alzheimer’s clinical syndrome and pathological changes.