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

Authors: Ferschmann, Christian; Messerschmidt, Konstantin; Gnörich, Johannes; Barthel, Henryk; Marek, Ken; Palleis, Carla; Katzdobler, Sabrina; +24 Authors

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

Abstract

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.

Keywords

Male, Nortropanes, Dopamine, tau Proteins, 4R-Tau, Female [MeSH] ; 4R-Tau ; Aged [MeSH] ; Tomography, Emission-Computed, Single-Photon [MeSH] ; Humans [MeSH] ; Motor reserve ; Middle Aged [MeSH] ; Tauopathies/metabolism [MeSH] ; Nortropanes/pharmacokinetics [MeSH] ; Original Article ; Tauopathies/diagnostic imaging [MeSH] ; Dopamine/metabolism [MeSH] ; DaT imaging ; Male [MeSH] ; Positron-Emission Tomography [MeSH] ; Dopamine Plasma Membrane Transport Proteins/metabolism [MeSH] ; [ ; tau Proteins/metabolism [MeSH], diagnostic imaging [Tauopathies], Humans, metabolism [Dopamine], Aged, Tomography, Emission-Computed, Single-Photon, Dopamine Plasma Membrane Transport Proteins, Motor reserve, Middle Aged, pharmacokinetics [Nortropanes], metabolism [tau Proteins], [18F]PI-2620 tau-PET, Tauopathies, Positron-Emission Tomography, metabolism [Dopamine Plasma Membrane Transport Proteins], Original Article, Female, metabolism [Tauopathies], DaT imaging, ddc: ddc:610

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
4
Top 10%
Average
Average
Green
hybrid
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