期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-28896-3
关键词
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资金
- European Reference Network for Rare Neurological Diseases [739510]
- NIH [P30AG010124, P01AG066597, U19AG062418, R01-NS109260]
- National Center for Advancing Translational Sciences [TL1TR001880]
- German Research Foundation (DFG) [SCHR 774/5-1, INST 409/193-1 FUGG, 390857198]
- Hertie foundation for clinical neurosciences
- Rossy Foundation
- Safra Foundation
- Deutsche Forschungsgemeinschaft (DFG) [HO2402/18-1 MSAomics]
- German Federal Ministry of Education and Research (BMBF) [01EK1605A HitTau]
- VolkswagenStiftung
- Petermax-Muller Foundation
- Hirnliga e.V. (Manfred-Strohscheer-Stiftung)
- Alzheimer Forschung Initiative e.V. [19063p]
- Lower Saxony Ministry for Science (Niedersachsisches Vorab)
The present study combines tau-PET, resting-state fMRI, and histopathology data to demonstrate the association between brain connectivity and tau deposition patterns in 4-repeat tauopathies.
Tau pathology is the main driver of neuronal dysfunction in 4-repeat tauopathies, including cortico-basal degeneration and progressive supranuclear palsy. Tau is assumed to spread prion-like across connected neurons, but the mechanisms of tau propagation are largely elusive in 4-repeat tauopathies, characterized not only by neuronal but also by astroglial and oligodendroglial tau accumulation. Here, we assess whether connectivity is associated with 4R-tau deposition patterns by combining resting-state fMRI connectomics with both 2(nd) generation F-18-PI-2620 tau-PET in 46 patients with clinically diagnosed 4-repeat tauopathies and post-mortem cell-type-specific regional tau assessments from two independent progressive supranuclear palsy patient samples (n = 97 and n = 96). We find that inter-regional connectivity is associated with higher inter-regional correlation of both tau-PET and post-mortem tau levels in 4-repeat tauopathies. In regional cell-type specific post-mortem tau assessments, this association is stronger for neuronal than for astroglial or oligodendroglial tau, suggesting that connectivity is primarily associated with neuronal tau accumulation. Using tau-PET we find further that patient-level tau patterns are associated with the connectivity of subcortical tau epicenters. Together, the current study provides combined in vivo tau-PET and histopathological evidence that brain connectivity is associated with tau deposition patterns in 4-repeat tauopathies. Tau pathology drives neuronal dysfunction in 4- repeat tauopathies. Here, the authors combine tau-PET, resting-state fMRI and histopathology data, to show that brain connectivity is associated with tau deposition patterns in 4-repeat tauopathies.
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