PT  - JOURNAL ARTICLE
AU  - Giorgio, Joseph
AU  - Soleimani-Meigooni, David N.
AU  - Janabi, Mustafa
AU  - Baker, Suzanne L.
AU  - Chen, Xi
AU  - Toueg, Tyler N.
AU  - Weimer, Robby
AU  - Zinnhardt, Bastian
AU  - Green, Ari
AU  - Rabinovici, Gil D.
AU  - Jagust, William J.
TI  - Imaging Synaptic Density in Aging and Alzheimer Disease with [<sup>18</sup>F]SynVesT-1
AID  - 10.2967/jnumed.124.269005
DP  - 2025 Apr 01
TA  - Journal of Nuclear Medicine
PG  - 620--625
VI  - 66
IP  - 4
4099  - http://jnm.snmjournals.org/content/66/4/620.short
4100  - http://jnm.snmjournals.org/content/66/4/620.full
SO  - J Nucl Med2025 Apr 01; 66
AB  - Synaptic density imaging with PET is a relatively new approach to monitoring synaptic injury in neurodegenerative diseases. However, there are remaining technical and clinical questions, including questions on reference region selection and on how specific phenotypic presentations and symptoms of Alzheimer disease (AD) are reflected in alterations in synaptic density. Methods: Using a synaptic vesicle glycoprotein 2A (SV2A) PET ligand radiolabeled with the 18F isotope ([18F]SynVesT-1), we performed sensitivity analyses to determine the optimal reference tissue modeling approach to derive whole-brain ratio images. Using these whole-brain images from a sample of young adults, older adults, and patients with varied phenotypic presentations of AD, we then contrasted regional SV2A density and in vivo AD biomarkers. Results: Reference tissue optimization concluded that a cerebellar gray matter reference region is best for deriving whole-brain ratio images. Using these images, we found a strong inverse association between [18F]SynVesT-1 PET uptake and amyloid β and tau PET deposition. Finally, we found that individuals with a lower temporal gray matter volume but higher temporal [18F]SynVesT-1 PET uptake show preserved performance on the mini-mental state examination. Conclusion: [18F]SynVesT-1 PET shows a close association with in vivo AD pathology, and preserved SV2A density may be a possible marker for resilience to neurodegeneration.