Objective: Our study aimed to elucidate the impact of tau depositions on brain microstructure and macrostructure in progressive supranuclear palsy (PSP).

Background: The link between tau accumulation and structural changes in PSP remains unclear. Here, we examined the association between tau pathology, tissue connectivity (TC), and structural volumes (VOLs) in patients with PSP compared with Alzheimer’s disease (AD) cases and healthy controls (HCs) using MRI and tau positron emission tomography (PET).

Method: Participants

Thirty-six patients with PSP (mean PSP rating scale score ± SD, 41.2 ± 17.5), thirty-two age-matched patients with AD (mean Mini-Mental State Examination score ± SD, 21.9 ± 3.3), and forty-six age-matched HCs were recruited. The diagnosis was supported by visual reads of [11C] PiB amyloid PET.

Image analysis

All subjects underwent tau PET with florzolotau (18F). They also received diffusion tensor and T1-weighted imaging to measure TC and VOLs, respectively. Tau depositions were evaluated as regional radiotracer retentions and AI-determined PSP tau score (Endo H et al., Mov Disord 2022). Since abnormal diffusivity has been reported in the superior cerebellar peduncles, the corpus callosum body, and the superior longitudinal fasciculus (SLF) of PSP cases, we examined correlations of TC in these fiber paths with tau loads and VOLs in multiple parcels.

Results: The mean diffusivity (MD) of the left SLF in PSP was significantly higher than that in AD or HCs and positively correlated with PSP tau score (Pearson’s r = 0.54, p < 0.001) and tau tracer retentions in the left midbrain (r = 0.44, p = 0.01), globus pallidus (r = 0.37, p = 0.03), thalamus (r = 0.41, p = 0.01), superior frontal gyrus (r = 0.48, p = 0.003), and precentral gyrus (r = 0.41, p = 0.013). The MD also negatively correlated with the left angular gyrus VOL (r = -0.36, p = 0.031).

Conclusion: The SLF could be involved as a pathway in the subcortical-to-frontal expansion of PSP tau pathologies, and consequent tau depositions in the left frontal lobe may lead to neurodegeneration in the left angular gyrus through disrupted SLF connections between these areas. The left-predominant pathologies are likely to arise from the well-known left-right structural asymmetry of the SLF.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/key-neural-tracts-involved-in-tau-depositions-and-neurodegeneration-as-revealed-by-multimodal-mri-and-pet-assays-in-progressive-supranuclear-palsy/