[11C]UCB-J PET imaging of synaptic vesicle protein SV2A in cognitive decline

1538 Objectives: [11C]UCB-J is a PET radioligand which specifically binds to synaptic vesicle protein SV2A and is designed to reflect synaptic density. As synaptic loss is a hallmark of neurodegenerative diseases, PET imaging can provide for an in vivo analysis of synaptic density changes in Alzheimer’s Disease (AD). The purpose of this work is to investigate changes in [11C]UCB-J uptake in unique dementia cases across the clinical and pathological spectrum of AD. Methods: [11C]UCB-J dynamic PET imaging was conducted over 70 minutes in fifteen participants recruited from the UW ADRC. Amyloid (A+/-) and tau (T+/-) status was determined using [11C]PiB and [18F]MK-6240 PET scans, respectively. The participants included eleven CU (A-/T-), one CU (A+/T+), one MCI (A-/T-), one non-AD dementia (A-/T-), and one clinically-diagnosed AD with unknown amyloid and tau status (scans pending). Multiple ROIs were taken using FreeSurfer templates acquired using individual T1w MR images: hippocampus, entorhinal cortex, parahippocampus, frontal cortex, and the parietal cortex. Regional DVRs were calculated using SRTM2 with t* = 35min and a global clearance rate for the cerebellar reference region k’2fixed to a set of values which ranged from 0.01 to 1.0 min-1 with an increment of 0.01. Results: Relative to the CU (A-/T-) DVR, [11C]UCB-J DVR measures in the hippocampus were decreased in the CU (A+/T+), MCI (A-/T-), non-AD dementia (A-/T-), and AD (A?/T?) cases with 0.71, 0.52, 0.55, and 0.36 compared to 0.88±0.13 in CU. The parahippocampus also showed decreases in the MCI (A-/T-), non-AD dementia (A-/T-), and AD (A?/T?) cases (0.71, 0.43, 0.64 vs 0.90±0.14). The CU (A+/T+) and the non-AD dementia (A-/T-) subjects showed lower DVR values in the inferior parietal lobe (1.10, 1.14 vs 1.34±0.11) as well as in the medial frontal lobe (1.20, 1.14 vs 1.34±0.11). Decreases in the entorhinal cortex were also seen in the non-AD dementia (A-/T-) and the AD (A?/T?) cases (0.52, 0.34 vs 0.80±0.17). Conclusions: For all four subjects in cognitive decline, [11C]UCB-J binding is reduced in the hippocampus when compared to the cognitively unimpaired A-/T- subjects. Decreased binding in the parahippocampus, inferior parietal lobe, medial frontal lobe, and/or the entorhinal cortex was also observed in some of those cases. Ongoing, longitudinal studies with larger sample sizes will investigate associations between cognitive, amyloid, and tau status with [11C]UCB-J measured synaptic density.