CSF SNAP‐25 Correlations with Synaptic Density by [11C]‐UCB‐J‐PET Imaging and AD Biomarkers

Background Synaptic dysfunction occurs prior to neuronal loss in the early stages of AD. A biomarker reflective of these changes could indicate AD before clinical manifestations. SNAP‐25 is a potential candidate, but the relationship between SNAP‐25 and established AD biomarkers is unclear. Further investigation is needed to determine the utility of this biomarker during the pre‐clinical phase. Method SNAP‐25 was measured using the Quanterix Single molecule array platform. A partial validation was conducted to evaluate assay performance in CSF and EDTA plasma. A cross‐sectional pilot study was then performed by measuring SNAP‐25 in CSF from 54 participants in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) and Wisconsin Alzheimer’s Disease Research Center (WI‐ADRC) cohorts. SV2A synaptic density was measured in each participant using [11C]‐UCB‐J‐PET. Amyloid and tau status was determined in a subset of the group using [11C]‐PiB (N = 52) and [18F]‐MK6240‐PET (N = 44), respectively. Additional CSF biomarkers (Aß42, pTau‐181, and tTau) were measured using the Roche Cobas e601 Elecsys platform. A confirmatory study was performed with 80 additional WRAP and WI‐ADRC participants (53A+, 27 A‐). These participants did not have [11C]‐UCB‐J‐PET imaging. Result The SNAP‐25 assay demonstrated excellent precision (