Objective: Find the relations between normative FC and seed-to-seed correlations in pathological tau load. Model the FC maps for twelve patients, using post-mortem tau pathology data. Calculate transition FC maps between different stages of PSP.

Background: Progressive Supranuclear Palsy (PSP) is characterized by atrophy of the basal ganglia and midbrain in a staged manner.¹ Although tau spread is associated with functional connectivity (FC) as measured with tau-PET deposition,² the progression of neuropathological stages needs further exploration.

Method: We obtained normative FC maps for specific seed regions of interest from 53 resting state functional-MRI images of age-matched healthy controls from the ADNI (Alzheimer’s Disease Neuroimaging Initiative) database, preprocessed with DPARSF Matlab toolbox. We then calculate the correlations between normative seed-to-seed connectivity strength and seed-to-seed correlations in post-mortem tau load. Dysconnectivity maps were modelled from 12 PSP autopsy cases-tau load that was collected in the following regions (seeds): substantia nigra (SN), subthalamic nucleus (STN), dentate nucleus, globus pallidus, striatum, middle-frontal gyrus. Normative FC maps from each seed were multiplied by the tau load found in each patient’s corresponding region, and these adjusted FC maps are summed to generate a composite dysconnectivity map. Statistical parametric mapping was used to regress FC-maps and to obtain transition maps between each PSP stage.

Results: We found a weak association between connectivity strength and tau deposition that did not achieve statistical significance. We generated estimated FC maps for twelve PSP-cases (3 cases in stage I-II, 5 cases stage III-IV, and 4 cases in stages V-VI) and estimated transition stage FC maps that showed a predominance of SN and STN tau load in early stages. Later stages are characterized by tau deposition in regions that have high connectivity with SN/STN.

Conclusion: The results of the networks affected might explain the spread of tau pathology in PSP. It also supports the usefulness of fMRI to model the severity of neuropathological involvement. A future analysis may investigate increased sample size to strengthen the association between FC and tau spread, as well as explore using fMRIs of PSP patients. We expect that the stage-specific FC maps from one seed can predict tau load in another region with prediction accuracy measured by goodness of fit statistics.

References: 1. Kovacs GG, Lukic MJ, Irwin DJ, et al. Distribution patterns of tau pathology in progressive supranuclear palsy. Acta Neuropathol. 08 2020;140(2):99-119. doi:10.1007/s00401-020-02158-2
2. Franzmeier N, Brendel M, Beyer L, et al. Tau deposition patterns are associated with functional connectivity in primary tauopathies. Nat Commun. Mar 15 2022;13(1):1362. doi:10.1038/s41467-022-28896-3

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MDS Abstracts - https://www.mdsabstracts.org/abstract/connectome-of-pathology-stages-of-progressive-supranuclear-palsy/