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  Tau accumulation is associated with dopamine deficiency in vivo in four-repeat tauopathies

Ferschmann, C., Messerschmidt, K., Gnörich, J., Barthel, H., Marek, K., Palleis, C., et al. (2024). Tau accumulation is associated with dopamine deficiency in vivo in four-repeat tauopathies. European Journal of Nuclear Medicine and Molecular Imaging, 51(7), 1909-1922. doi:10.1007/s00259-024-06637-6.

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 Creators:
Ferschmann, Christian1, Author
Messerschmidt, Konstantin2, Author
Gnörich, Johannes1, Author
Barthel, Henryk2, Author
Marek, Ken3, 4, Author
Palleis, Carla5, 6, 7, Author
Katzdobler, Sabrina7, Author
Stockbauer, Anna7, Author
Fietzek, Urban7, Author
Finze, Anika1, Author
Biechele, Gloria1, 8, Author
Rumpf, Jost-Julian9, Author
Saur, Dorothee9, Author
Schroeter, Matthias L.10, 11, 12, Author                 
Rullmann, Michael2, Author
Beyer, Leonie1, Author
Eckenweber, Florian1, Author
Wall, Stephan1, Author
Schildan, Andreas2, Author
Patt, Marianne2, Author
Stephens, Andrew13, AuthorClassen, Joseph9, AuthorBartenstein, Peter1, 5, AuthorSeibyl, John3, 4, AuthorFranzmeier, Nicolai5, 14, AuthorLevin, Johannes5, 6, 7, AuthorHöglinger, Günter U.6, 7, AuthorSabri, Osama2, AuthorBrendel, Matthias1, 5, 6, AuthorScheifele, Maximilian1, AuthorGerman Imaging Initiative for Tauopathies (GII4T), Author               more..
Affiliations:
1Department of Nuclear Medicine, Ludwig Maximilians University Munich, Germany, ou_persistent22              
2Department of Nuclear Medicine, University of Leipzig, Germany, ou_persistent22              
3InviCRO, LLC, Boston, MA, USA, ou_persistent22              
4Molecular Neuroimaging, A Division of inviCRO, New Haven, CT, USA, ou_persistent22              
5Munich Cluster for Systems Neurology (SyNergy), Ludwig Maximilians University Munich, Germany, ou_persistent22              
6German Center for Neurodegenerative Diseases (DZNE), Munich, Germany, ou_persistent22              
7Department of Neurology, Ludwig Maximilians University Munich, Germany, ou_persistent22              
8Department of Radiology, Ludwig Maximilians University Munich, Germany, ou_persistent22              
9Department of Neurology, University Hospital Leipzig, Germany, ou_persistent22              
10Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              
11Leipzig Research Center for Civilization Diseases (LIFE), University of Leipzig, Germany, ou_persistent22              
12Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
13Life Molecular Imaging GmbH, Berlin, Germany, ou_persistent22              
14Institute for Stroke and Dementia Research (ISD), Ludwig Maximilians University Munich, Germany, ou_persistent22              

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Free keywords: 4R-Tau; DaT imaging; Motor reserve; [18F]PI-2620 tau-PET
 Abstract: Purpose: We hypothesized that severe tau burden in brain regions involved in direct or indirect pathways of the basal ganglia correlate with more severe striatal dopamine deficiency in four-repeat (4R) tauopathies. Therefore, we correlated [18F]PI-2620 tau-positron-emission-tomography (PET) imaging with [123I]-Ioflupane single-photon-emission-computed tomography (SPECT) for dopamine transporter (DaT) availability.

Methods: Thirty-eight patients with clinically diagnosed 4R-tauopathies (21 male; 69.0 ± 8.5 years) and 15 patients with clinically diagnosed α-synucleinopathies (8 male; 66.1 ± 10.3 years) who underwent [18F]PI-2620 tau-PET and DaT-SPECT imaging with a time gap of 3 ± 5 months were evaluated. Regional Tau-PET signals and DaT availability as well as their principal components were correlated in patients with 4R-tauopathies and α-synucleinopathies. Both biomarkers and the residuals of their association were correlated with clinical severity scores in 4R-tauopathies.

Results: In patients with 4R-tauopathies, [18F]PI-2620 binding in basal ganglia and midbrain regions was negatively associated with striatal DaT availability (i.e. globus pallidus internus and putamen (β = - 0.464, p = 0.006, Durbin-Watson statistics = 1.824) in a multiple regression model. Contrarily, [18F]PI-2620 binding in the dentate nucleus showed no significant regression factor with DaT availability in the striatum (β = 0.078, p = 0.662, Durbin-Watson statistics = 1.686). Patients with α-synucleinopathies did not indicate any regional associations between [18F]PI-2620-binding and DaT availability. Higher DaT-SPECT binding relative to tau burden was associated with better clinical performance (β = - 0.522, p = 0.011, Durbin-Watson statistics = 2.663) in patients with 4R-tauopathies.

Conclusion: Tau burden in brain regions involved in dopaminergic pathways is associated with aggravated dopaminergic dysfunction in patients with clinically diagnosed primary tauopathies. The ability to sustain dopamine transmission despite tau accumulation may preserve motor function.

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Language(s): eng - English
 Dates: 2023-07-112024-02-042024-02-172024-06
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1007/s00259-024-06637-6
Other: epub 2024
PMID: 38366196
 Degree: -

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Funding organization : Projekt DEAL

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Title: European Journal of Nuclear Medicine and Molecular Imaging
  Other : Eur. J. Nucl. Med. Mol. Imaging
Source Genre: Journal
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Publ. Info: Heidelberg, Germany : Springer-Verlag
Pages: - Volume / Issue: 51 (7) Sequence Number: - Start / End Page: 1909 - 1922 Identifier: ISSN: 1619-7070
CoNE: https://pure.mpg.de/cone/journals/resource/954925519624