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

Abstract:

ABSTRACT Understanding the cellular underpinnings of neurodegeneration remains a challenge; loss of synapses and dendritic arborisation are characteristic and can be quantified i n 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 (PSP-RS; n = 22) and amyloid-negative (determined by [ 11 C]PiB PET) Corticobasal 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 [ 11 C]UCB-J non-displaceable binding potential (BP ND ) in excess of atrophy. In PSP-RS and CBD separately, regional cortical ODI was significantly associated with [ 11 C]UCB-J BP ND 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. Furthermore, 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.