Simons, Mikael
Mayo Clinic
German Center for Neurodegenerative Diseases
Citations 2
Transport vehicle–mediated TREM2 PET maps myeloid cells in the glioblastoma microenvironment
Brendel, M., Feng, Ruoqing, Mueller, Katharina, Kössinger, Anna Laura, Teske, Nina C. , Greve, Thomas, Kirchleitner, Sabrina Viktoria, Nikolaishvili, Elene, Lorenz, Julia , Hoermann, Leonie , Kunze, Lea H. , Schaefer, Rebecca , Liu, Lu , Haertel, Marlies, Dhoqina, Dario , Gnörich, Johannes, Turhan, Sena Gül, Ertürk, Ali, Thevis, Justus Flinn, Park, Ha Eun, Wind, Karin , Lindheimer, Felix, Zenatti, Valerio , Prestel, Matthias , Lichtenthaler, Stefan, Werner, Rudolf, Riemenschneider, Markus, Kalasauskas, Darius , Schmutzer-Sondergeld, Michael, Stoecklein, Veit M. , Ringel, Florian , Meyer, Ana-Claire, Lewcock, Joseph W. , Monroe, Kathryn M. , Schlepckow, Kai , Haass, Christian, Herms, Jochen , Albert, Nathalie L. , Brendel, Matthias , Bartos, Laura M. , Mueller, K , Koessinger, Anna L. , Kirchleitner, Sabrina Viktoria , Blobner, Jens , Gnörich, Johannes , Müller, Stephan A. , Kolabas, Zeynep Ilgin , Ulukaya, Selin , Ertürk, Ali , Lindheimer, Felix , Bhat, Krishna , Tahirović, Sabina , Lichtenthaler, Stefan F. , Schmutzer-Sondergeld, Michael , Meyer, Ana-Claire, Haass, Christian , Baumgarten, Louisa von , Harter, Patrick N. , Simons, Mikael , Lindner, Simon
No container title available | February 11, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Glioblastomas exhibit low immunogenicity and a highly immunosuppressive tumor microenvironment (TME) mediated by both tumor cells and tumor associated microglia/macrophages (TAMs). However, biomarkers that allow for specific detection, monitoring and therapy response assessment of the TAM phenotype in glioblastoma are still lacking. To address this gap, we characterized the dynamics of TAM clusters in the TME of experimental SB28 glioblastoma using single-cell RNA sequencing, immunofluorescence, and molecular imaging and identified Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) as a dynamic TAM-specific target. Consequently, we investigated a novel 64 Cu-labeled TREM2 radiotracer with a blood-brain barrier transport vehicle for translational mapping of TAMs in the TME of glioblastoma. We found strong and highly myeloid cell-specific PET signals that followed the trajectory of TREM2 gene expression from early- towards late-stage tumors. Transient myeloid cell depletion via CSF1R inhibition showed a reduction of TREM2 PET signals compared to placebo and prolonged survival in SB28 glioblastoma mice, while TREM2 stimulation led to increased TREM2 PET signals. Translation into a pilot cohort of patients with glioblastoma revealed strong TREM2 PET signals predominantly at lesion edges and high heterogeneity across individuals, matching with immunohistochemistry. In summary, TREM2 PET imaging has strong potential as an immune cell-specific biomarker for personalized assessment of the TAM phenotype in the TME of patients with glioblastoma.
Pattern and implications of neurological examination findings in autosomal dominant Alzheimer disease
Vöglein, Jonathan , Morris, John C. , Dieterich, Marianne , Preische, Oliver, Hofmann, Anna, Hassenstab, Jason , Fagan, Anne M. , Noble, James M. , Berman, Sarah , Graff‐Radford, Neill R. , Farlow, Martin R. , Chhatwal, Jasmeer P. , Salloway, Stephen , Xiong, Chengjie , Cairns, Nigel J., Perrin, Richard J. , Day, Gregory S. , Mori, Hiroshi , Suzuki, Kazushi , Masters, Colin L. , Goate, Alison , Buckles, Virginia, Fox, Nick C. , Chrem, Patricio, Ringman, John M. , Yakushev, Igor , Laske, Christoph , Bateman, Randall J. , Network, for the Dominantly Inherited Alzheimer, Day, Gregory S , Bateman, Randall J , Masters, Colin L , Vöglein, Jonathan , Xiong, Chengjie , Fox, Nick C , Hassenstab, Jason , Morris, John C , Goate, Alison M , Berman, Sarah , Noble, James M , Franzmeier, Nicolai , McDade, Eric , Simons, Mikael , Benzinger, Tammie L.S. , Ghetti, Bernardino , Xiong, Chengjie , Karch, Celeste M. , Martins, Ralph N. , Sánchez‐Valle, Raquel , Shimada, Hiroyuki , Ikeuchi, Takeshi , Schofield, Peter R. , Allegri, Ricardo , Jucker, Mathias , Höglinger, Günter U. , Danek, Adrian , Network, for the Dominantly Inherited Alzheimer
Alzheimer's & Dementia | May 24, 2022 | Volume: 19 | Issue: 2 | Pages: 632-645
AbstractIntroductionAs knowledge about neurological examination findings in autosomal dominant Alzheimer disease (ADAD) is incomplete, we aimed to determine the frequency and significance of neurological examination findings in ADAD.MethodsFrequencies of neurological examination findings were compared between symptomatic mutation carriers and non mutation carriers from the Dominantly Inherited Alzheimer Network (DIAN) to define AD neurological examination findings. AD neurological examination findings were analyzed regarding frequency, association with and predictive value regarding cognitive decline, and association with brain atrophy in symptomatic mutation carriers.ResultsAD neurological examination findings included abnormal deep tendon reflexes, gait disturbance, pathological cranial nerve examination findings, tremor, abnormal finger to nose and heel to shin testing, and compromised motor strength. The frequency of AD neurological examination findings was 65.1%. Cross‐sectionally, mutation carriers with AD neurological examination findings showed a more than two‐fold faster cognitive decline and had greater parieto‐temporal atrophy, including hippocampal atrophy. Longitudinally, AD neurological examination findings predicted a significantly greater decline over time.DiscussionADAD features a distinct pattern of neurological examination findings that is useful to estimate prognosis and may inform clinical care and therapeutic trial designs.