Synaptic loss in primary tauopathies revealed by [11C]UCB-J positron emission tomography


Background Synaptic loss is a prominent and early feature of many neurodegenerative diseases. Objectives We tested the hypothesis that synaptic density is reduced in the primary tauopathies of progressive supranuclear palsy (PSP-Richardson’s syndrome) and amyloid-negative corticobasal syndrome (CBS). Methods Forty four participants (15 CBS, 14 PSP, and 15 age-/sex-/education-matched controls) underwent positron emission tomography (PET) with the radioligand [ 11 C]UCB-J, which binds to synaptic vesicle glycoprotein 2A (SV2A), a marker of synaptic density; participants also had 3T magnetic resonance imaging and clinical and neuropsychological assessment. Results Nine CBS patients had negative amyloid biomarkers determined by [ 11 C]PiB PET and hence were deemed likely to have corticobasal degeneration (CBD). Patients with PSP-Richardson’s syndrome and amyloid-negative CBS were impaired in executive, memory and visuospatial tasks. [ 11 C]UCB-J binding was reduced across frontal, temporal, parietal, and occipital lobes, cingulate, hippocampus, insula, amygdala and subcortical structures in both PSP and CBD patients compared to controls (p