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  Interplay of tau and functional network connectivity in progressive supranuclear palsy: A [18F]PI-2620 PET/MRI study

Aghakhanyan, G., Rullmann, M., Rumpf, J., Schroeter, M. L., Scherlach, C., Patt, M., et al. (2022). Interplay of tau and functional network connectivity in progressive supranuclear palsy: A [18F]PI-2620 PET/MRI study. European Journal of Nuclear Medicine and Molecular Imaging, 50(1), 103-114. doi:10.1007/s00259-022-05952-0.

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Aghakhanyan, Gayane1, 2, Author
Rullmann, M.1, Author
Rumpf, J.3, Author
Schroeter, Matthias L.4, 5, Author           
Scherlach, C.6, Author
Patt, M.1, Author
Brendel, M.7, Author
Koglin, N.8, Author
Stephens, A. W.8, Author
Classen, J.3, Author
Hoffmann, K. T.6, Author
Sabri, O.1, Author
Barthel, H.1, Author
1Department of Nuclear Medicine, University of Leipzig, Germany, ou_persistent22              
2Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Italy, ou_persistent22              
3Department of Neurology, University Hospital Leipzig, Germany, ou_persistent22              
4Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              
5Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
6Department of Neuroradiology, University of Leipzig, Germany, ou_persistent22              
7Department of Nuclear Medicine, Ludwig Maximilians University Munich, Germany, ou_persistent22              
8Life Molecular Imaging GmbH, Berlin, Germany, ou_persistent22              


Free keywords: [18F]PI-2620; Functional network connectivity; PET/MRI; Progressive supranuclear palsy; Resting-state functional MRI; Tauopathy
 Abstract: Purpose: Progressive supranuclear palsy (PSP) is primary 4-repeat tauopathy. Evidence spanning from imaging studies indicate aberrant connectivity in PSPs. Our goal was to assess functional connectivity network alterations in PSP patients and the potential link between regional tau-burden and network-level functional connectivity using the next-generation tau PET tracer [18F]PI-2620 and resting-state functional MRI (fMRI).

Material and methods: Twenty-four probable PSP patients (70.9 ± 6.9 years, 13 female), including 14 Richardson syndrome (RS) and 10 non-RS phenotypes, underwent [18F]PI-2620 PET/MRI imaging. Distribution volume ratios (DVRs) were estimated using non-invasive pharmacokinetic modeling. Resting-state fMRI was also acquired in these patients as well as in thirteen older non-AD MCI reference group (64 ± 9 years, 4 female). The functional network was constructed using 141 by 141 region-to-region functional connectivity metrics (RRC) and network-based statistic was carried out (connection threshold p < 0.001, cluster threshold pFDR < 0.05).

Results: In total, 9870 functional connections were analyzed. PSPs compared to aged non-AD MCI reference group expressed aberrant connectivity evidenced by the significant NBS network consisting of 89 ROIs and 118 connections among them (NBS mass 4226, pFDR < 0.05). Tau load in the right globus pallidus externus (GPe) and left dentate nucleus (DN) showed significant effects on functional network connectivity. The network linked with increased tau load in the right GPe was associated with hyperconnectivity of low-range intra-opercular connections (NBS mass 356, pFDR < 0.05), while the network linked with increased tau load in the left cerebellar DN was associated with cerebellar hyperconnectivity and cortico-cerebellar hypoconnectivity (NBS mass 517, pFDR < 0.05).

Conclusions: PSP patients show altered functional connectivity. Network incorporating deep gray matter structures demonstrate hypoconnectivity, cerebellum hyperconnectivity, while cortico-cortical connections show variable changes. Tau load in the right GPe and left DN is associated with functional networks which strengthen low-scale intra-opercular and intra-cerebellar connections and weaken opercular-cerebellar connections. These findings support the concept of tau load-dependent functional network changes in PSP, by that providing evidence for downstream effects of neuropathology on brain functionality in this primary tauopathy.


Language(s): eng - English
 Dates: 2021-12-162022-08-232022-09-012022-12
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1007/s00259-022-05952-0
Other: epub 2022
PMID: 36048259
 Degree: -



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Title: European Journal of Nuclear Medicine and Molecular Imaging
  Other : Eur. J. Nucl. Med. Mol. Imaging
Source Genre: Journal
Publ. Info: Heidelberg, Germany : Springer-Verlag
Pages: - Volume / Issue: 50 (1) Sequence Number: - Start / End Page: 103 - 114 Identifier: ISSN: 1619-7070
CoNE: https://pure.mpg.de/cone/journals/resource/954925519624