%0 Journal Article
%T Synaptic Loss in Primary Tauopathies Revealed by [11 C]UCB-J Positron Emission Tomography.
%A Holland N
%A Jones PS
%A Savulich G
%A Wiggins JK
%A Hong YT
%A Fryer TD
%A Manavaki R
%A Sephton SM
%A Boros I
%A Malpetti M
%A Hezemans FH
%A Aigbirhio FI
%A Coles JP
%A O'Brien J
%A Rowe JB
%J Mov Disord
%V 35
%N 10
%D 10 2020
%M 32652635
%F 9.698
%R 10.1002/mds.28188
%X Synaptic loss is a prominent and early feature of many neurodegenerative diseases.<BR>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).<BR>Forty-four participants (15 CBS, 14 PSP, and 15 age-/sex-/education-matched controls) underwent PET with the radioligand [11 C]UCB-J, which binds to synaptic vesicle glycoprotein 2A, a marker of synaptic density; participants also had 3 Tesla MRI and clinical and neuropsychological assessment.<BR>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 < 0.01), with median reductions up to 50%, consistent with postmortem data. Reductions of 20% to 30% were widespread even in areas of the brain with minimal atrophy. There was a negative correlation between global [11 C]UCB-J binding and the PSP and CBD rating scales (R = -0.61, P < 0.002; R = -0.72, P < 0.001, respectively) and a positive correlation with the revised Addenbrooke's Cognitive Examination (R = 0.52; P = 0.01).<BR>We confirm severe synaptic loss in PSP and CBD in proportion to disease severity, providing critical insight into the pathophysiology of primary degenerative tauopathies. [11 C]UCB-J may facilitate treatment strategies for disease-modification, synaptic maintenance, or restoration. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.