In vivo coupling of dendritic complexity with presynaptic density in primary tauopathies

Understanding the cellular underpinnings of neurodegeneration remains a challenge; loss of synapses and dendritic arborization are characteristic and can be quantified in vivo, with [11(C)]UCB-J PET and MRI-based Orientation Dispersion Imaging (ODI), respectively. We aimed to assess how both measures are correlated, in 4R-tauopathies of progressive supranuclear palsy - Richardson's Syndrome (PSP-RS; n = 22) and amyloid-negative (determined by [C-11]PiB PET) Corticobasal Syndrome (Cortiobasal degeneration, CBD; n =14), as neurodegenerative disease models, in this proof-of-concept study. Compared to controls (n = 27), PSP-RS and CBD patients had widespread reductions in cortical ODI, and [C-11]UCB-J non-displaceable binding potential (BPND) in excess of atrophy. In PSP-RS and CBD separately, regional cortical ODI was significantly associated with [C-11]UCB-J BPND in disease-associated regions (p < 0.05, FDR corrected). Our findings indicate that reductions in synaptic density and dendritic complexity in PSP-RS and CBD are more severe and extensive than atrophy. Further-more, both measures are tightly coupled in vivo, furthering our understanding of the pathophysiology of neurodegeneration, and applicable to studies of early neurodegeneration with a safe and widely available MRI platform. (C) 2021 The Author(s). Published by Elsevier Inc.

Automated summary

The study found that patients with PSP-RS and CBD have widespread reductions in cortical ODI and non-displaceable binding potential of [C-11]UCB-J, which are more severe and extensive than atrophy. Regional cortical ODI was significantly associated with [C-11]UCB-J BPND in disease-associated regions. This furthers our understanding of the pathophysiology of neurodegeneration.