Publications

@article{Kling2025,

title = {Exploring the origins of frequent tau-PET signal in vermal and adjacent regions},

author = {Agnes Kling and Julia Kusche-Palenga and Carla Palleis and Alexander Jäck and Alexander M. Bernhardt and Lukas Frontzkowski and Sebastian N. Roemer and Luna Slemann and Mirlind Zaganjori and Maximilian Scheifele and Lars Paeger and Gérard N. Bischof and Thilo van Eimeren and Alexander Drzezga and Osama Sabri and Michael Rullmann and Henryk Barthel and Johannes Levin and Jochen Herms and Nicolai Franzmeier and Günter Höglinger and Sigrun Roeber and Matthias Brendel and Johannes Gnörich},

doi = {10.1007/s00259-025-07199-x},

issn = {1619-7089},

year  = {2025},

date = {2025-03-18},

urldate = {2025-03-18},

journal = {Eur J Nucl Med Mol Imaging},

publisher = {Springer Science and Business Media LLC},

abstract = {<jats:title>Abstract</jats:title>

          <jats:sec>

            <jats:title>Purpose</jats:title>

            <jats:p>Off-target binding remains a significant challenge in tau-PET neuroimaging. While off-targets including monoamine oxidase enzymes and neuromelanin-containing cells have been identified, recent studies indicated a relevant binding of novel tau tracers to melanin-containing structures. To date, little is known about the effect of melanocytes in the meninges on tracer signals in brain PET data. Thus, we aimed to identify the target structure causal for the frequently observed [<jats:sup>18</jats:sup>F]PI-2620 PET signal in the vermis and adjacent cerebellar regions.</jats:p>

          </jats:sec>

          <jats:sec>

            <jats:title>Methods</jats:title>

            <jats:p>274 participants underwent dynamic [<jats:sup>18</jats:sup>F]PI-2620 tau-PET: 3/4R-tauopathies (n = 85), 4R-tauopathies (n = 147), tau-negative disease controls (n = 24), and healthy controls (n = 18). Standardized uptake value ratio (SUVR) and kinetic parameters including the distribution volume ratio (DVR), tracer clearance (k2) and relative perfusion (R1), were compared among the cohorts and sexes using the Automated Anatomical Labelling (AAL) atlas. Age and p-Tau levels in cerebrospinal fluid (CSF) were assessed for their relationship with vermal tau-PET signal. Furthermore, we combined autoradiographic and histochemical experiments on post-mortem brain tissue of deceased patients (n = 9).</jats:p>

          </jats:sec>

          <jats:sec>

            <jats:title>Results</jats:title>

            <jats:p>Male participants revealed higher mean vermal [<jats:sup>18</jats:sup>F]PI-2620 DVR (0.95 ± 0.13; vs. females 0.88 ± 0.10, p < 0.0001). Sex-related differences were most pronounced in the 3/4R-tauopathy cohort (p < 0.0001). Mean SUVR<jats:sub>Ver/Cbl</jats:sub>, k2 and correlation analyses of kinetic parameters did not differ among groups. Histological assessments revealed co-localization of leptomeningeal pigmented cells with strong autoradiography signal spots within the vermal fissures. Tau-related autoradiography signals, age or p-Tau levels did not correlate significantly with tau-PET signals. Iron deposits did not cause relevant autoradiography signals in the vermis.</jats:p>

          </jats:sec>

          <jats:sec>

            <jats:title>Conclusion</jats:title>

            <jats:p>Leptomeningeal melanocytes are the primary target structure for [<jats:sup>18</jats:sup>F]PI-2620 PET binding in anterior vermis, whereas iron and tau deposits do not contribute significantly.

</jats:p>

          </jats:sec>},

keywords = {Iron, Sex differences, Signal sources, Tau PET},

pubstate = {published},

tppubtype = {article}

}

@article{Slemann2024,

title = {Neuronal and oligodendroglial, but not astroglial, tau translates to in vivo tau PET signals in individuals with primary tauopathies},

author = {Luna Slemann and Johannes Gnörich and Selina Hummel and Laura M. Bartos and Carolin Klaus and Agnes Kling and Julia Kusche-Palenga and Sebastian T. Kunte and Lea H. Kunze and Amelie L. Englert and Yunlei Li and Letizia Vogler and Sabrina Katzdobler and Carla Palleis and Alexander Bernhardt and Alexander Jäck and Andreas Zwergal and Franziska Hopfner and Sebastian N. Roemer-Cassiano and Gloria Biechele and Sophia Stöcklein and Gerard Bischof and Thilo van Eimeren and Alexander Drzezga and Osama Sabri and Henryk Barthel and Gesine Respondek and Timo Grimmer and Johannes Levin and Jochen Herms and Lars Paeger and Marie Willroider and Leonie Beyer and Günter U. Höglinger and Sigrun Roeber and Nicolai Franzmeier and Matthias Brendel},

doi = {10.1007/s00401-024-02834-7},

issn = {1432-0533},

year  = {2024},

date = {2024-12-00},

urldate = {2024-12-00},

journal = {Acta Neuropathol},

volume = {148},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {<jats:title>Abstract</jats:title><jats:p>Tau PET has attracted increasing interest as an imaging biomarker for 4-repeat (4R)-tauopathy progressive supranuclear palsy (PSP). However, the translation of in vitro 4R-tau binding to in vivo tau PET signals is still unclear. Therefore, we performed a translational study using a broad spectrum of advanced methodologies to investigate the sources of [<jats:sup>18</jats:sup>F]PI-2620 tau PET signals in individuals with 4R-tauopathies, including a pilot PET autopsy study in patients. First, we conducted a longitudinal [<jats:sup>18</jats:sup>F]PI-2620 PET/MRI study in a 4-repeat-tau mouse model (PS19) and detected elevated [<jats:sup>18</jats:sup>F]PI-2620 PET signals in the presence of high levels of neuronal tau. An innovative approach involving cell sorting after radiotracer injection in vivo revealed higher tracer uptake in single neurons than in the astrocytes of PS19 mice. Regional [<jats:sup>18</jats:sup>F]PI-2620 tau PET signals during the lifetime correlated with the abundance of fibrillary tau and with autoradiography signal intensity in PSP patients and disease controls who underwent autopsy 2–63 months after tau PET. In autoradiography, tau-positive neurons and oligodendrocytes with a high AT8 density, but not tau-positive astrocytes, were the drivers of [<jats:sup>18</jats:sup>F]PI-2620 autoradiography signals in individuals with PSP. The high tau abundance in oligodendrocytes at the boundary of gray and white matter facilitated the identification of an optimized frontal lobe target region to detect the tau burden in patients with PSP. In summary, neuronal and oligodendroglial tau constitutes the dominant source of tau PET radiotracer binding in 4-repeat-tauopathies, translating to an in vivo signal.</jats:p>},

keywords = {Signal sources, Tau PET, Tauopathy},

pubstate = {published},

tppubtype = {article}

}