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Researchers developed a method to count intact brain synapses in post-mortem tissue and validated that PET imaging with [11C]UCB-J accurately measures synapse loss in living patients. Studying six progressive supranuclear palsy (PSP) patients and six controls across 11 brain regions, they found that synapse loss was widespread and region-specific in PSP, correlated with tau pathology burden, and matched the reduction in PET signals obtained before death. Cortical synaptic density also correlated with cognitive function measured before death.
Why it matters
This validation supports [11C]UCB-J PET imaging as a reliable biomarker for tracking synapse loss in living patients with neurodegenerative diseases, potentially enabling earlier diagnosis and better monitoring of disease progression or treatment responses in conditions like PSP and other tauopathies.
⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Synapse loss is an early feature of neurodegeneration and may provide sensitive biomarkers for experimental medicine. Positron emission tomography (PET) with the synaptic vesicle glycoprotein 2A radioligand [11C]UCB-J shows widespread signal reduction across dementias. However, it remains unclear which aspects of synaptic integrity [11C]UCB-J PET measures. We developed a histological-imaging pipeline to quantify structurally intact synapses in post-mortem brain tissue. We applied it to six donors with the tauopathy progressive supranuclear palsy (PSP) who had ante-mortem [11C]UCB-J-PET, alongside six controls across 11 brain regions. Synapse loss in PSP was widespread but region-specific across cortical, subcortical, and brainstem regions. Greater synapse loss was associated with higher tau burden and pathology, and cortical synaptic density correlated with ante-mortem cognition. Post-mortem synaptic density correlated with in vivo [11C]UCB-J-PET signal. This study provides validation of SV2A PET as a biomarker of synaptic density and supports integration of imaging with histopathology in neurodegenerative disease research.