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

Abstract

A newly developed SV2A radiotracer, ¹⁸F-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 ¹⁸F-SynVesT-1 PET/MR and ¹⁸F-florbetapir PET/CT scans. Additionally, a subgroup of individuals also underwent ¹⁸F-MK-6240, ¹⁸F-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 ¹⁸F-SynVesT-1, and its close correlation with “A/T/N” biomarkers in patients with both Alzheimer’s clinical syndrome and pathological changes.