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Author: Christian Haass2
Distinct molecular profiles of skull bone marrow in health and neurological disorders.

Abstract (Expand)

The bone marrow in the skull is important for shaping immune responses in the brain and meninges, but its molecular makeup among bones and relevance in human diseases remain unclear. Here, we show that … the mouse skull has the most distinct transcriptomic profile compared with other bones in states of health and injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals that the skull marrow is the most distinct, with differentially expressed neutrophil-related pathways and a unique synaptic protein signature. 3D imaging demonstrates the structural and cellular details of human skull-meninges connections (SMCs) compared with veins. Last, using translocator protein positron emission tomography (TSPO-PET) imaging, we show that the skull bone marrow reflects inflammatory brain responses with a disease-specific spatial distribution in patients with various neurological disorders. The unique molecular profile and anatomical and functional connections of the skull show its potential as a site for diagnosing, monitoring, and treating brain diseases.

Authors: Zeynep Ilgin Kolabas, Louis B Kuemmerle, Robert Perneczky, Benjamin Förstera, Selin Ulukaya, Mayar Ali, Saketh Kapoor, Laura M Bartos, Maren Büttner, Ozum Sehnaz Caliskan, Zhouyi Rong, Hongcheng Mai, Luciano Höher, Denise Jeridi, Muge Molbay, Igor Khalin, Ioannis K Deligiannis, Moritz Negwer, Kenny Roberts, Alba Simats, Olga Carofiglio, Mihail I Todorov, Izabela Horvath, Furkan Ozturk, Selina Hummel, Gloria Biechele, Artem Zatcepin, Marcus Unterrainer, Johannes Gnörich, Jay Roodselaar, Joshua Shrouder, Pardis Khosravani, Benjamin Tast, Lisa Richter, Laura Díaz-Marugán, Doris Kaltenecker, Laurin Lux, Ying Chen, Shan Zhao, Boris-Stephan Rauchmann, Michael Sterr, Ines Kunze, Karen Stanic, Vanessa W Y Kan, Simon Besson-Girard, Sabrina Katzdobler, Carla Palleis, Julia Schädler, Johannes C Paetzold, Sabine Liebscher, Anja E Hauser, Özgün Gökçe, Heiko Lickert, Hanno Steinke, Corinne Benakis, Christian Braun, Celia P Martinez-Jimenez, Katharina Buerger, Nathalie L Albert, Günter Höglinger, Johannes Levin, Christian Haass, Anna Kopczak, Martin Dichgans, Joachim Havla, Tania Kümpfel, Martin Kerschensteiner, Martina Schifferer, Mikael Simons, Arthur Liesz, Natalie Krahmer, Omer A Bayraktar, Nicolai Franzmeier, Nikolaus Plesnila, Suheda Erener, Victor G Puelles, Claire Delbridge, Harsharan Singh Bhatia, Farida Hellal, Markus Elsner, Ingo Bechmann, Benjamin Ondruschka, Matthias Brendel, Fabian J Theis, Ali Ertürk

Date Published: 17th Aug 2023

Publication Type: Journal

Fibrillar Abeta triggers microglial proteome alterations and dysfunction in Alzheimer mouse models.

Abstract (Expand)

Microglial dysfunction is a key pathological feature of Alzheimer's disease (AD), but little is known about proteome-wide changes in microglia during the course of AD and their functional consequences. … Here, we performed an in-depth and time-resolved proteomic characterization of microglia in two mouse models of amyloid beta (Abeta) pathology, the overexpression APPPS1 and the knock-in APP-NL-G-F (APP-KI) model. We identified a large panel of Microglial Abeta Response Proteins (MARPs) that reflect heterogeneity of microglial alterations during early, middle and advanced stages of Abeta deposition and occur earlier in the APPPS1 mice. Strikingly, the kinetic differences in proteomic profiles correlated with the presence of fibrillar Abeta, rather than dystrophic neurites, suggesting that fibrillar Abeta may trigger the AD-associated microglial phenotype and the observed functional decline. The identified microglial proteomic fingerprints of AD provide a valuable resource for functional studies of novel molecular targets and potential biomarkers for monitoring AD progression or therapeutic efficacy.

Authors: L. Sebastian Monasor, S. A. Muller, A. V. Colombo, G. Tanrioever, J. Konig, S. Roth, A. Liesz, A. Berghofer, A. Piechotta, M. Prestel, T. Saito, T. C. Saido, J. Herms, M. Willem, C. Haass, S. F. Lichtenthaler, S. Tahirovic

Date Published: 8th Jun 2020

Publication Type: Journal

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