@article{e840ede769cb410e91939aa4b29d28d2,
title = "TREM2 modulates differential deposition of modified and non-modified Aβ species in extracellular plaques and intraneuronal deposits",
abstract = "Progressive accumulation of Amyloid-β (Aβ) deposits in the brain is a characteristic neuropathological hallmark of Alzheimer{\textquoteright}s disease (AD). During disease progression, extracellular Aβ plaques undergo specific changes in their composition by the sequential deposition of different modified Aβ species. Microglia are implicated in the restriction of amyloid deposits and play a major role in internalization and degradation of Aβ. Recent studies showed that rare variants of the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) are associated with an increased risk for AD. Post-translational modifications of Aβ could modulate the interaction with TREM2, and the uptake by microglia. Here, we demonstrate that genetic deletion of TREM2 or expression of a disease associated TREM2 variant in mice lead to differential accumulation of modified and non-modified Aβ species in extracellular plaques and intraneuronal deposits. Human brains with rare TREM2 AD risk variants also showed altered deposition of modified Aβ species in the different brain lesions as compared to cases with the common variant of TREM2. These findings indicate that TREM2 plays a critical role in the development and the composition of Aβ deposits, not only in extracellular plaques, but also intraneuronally, that both could contribute to the pathogenesis of AD.",
keywords = "Aβ, Intraneuronal, Microglia, Post-translational modification, TREM2, Vascular deposits",
author = "Pranav Joshi and Florian Riffel and Sathish Kumar and N{\`a}dia Villacampa and Sandra Theil and Samira Parhizkar and Christian Haass and Marco Colonna and Heneka, {Michael T.} and Thomas Arzberger and Jochen Herms and Jochen Walter",
note = "Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft, Grant WA1477/6-6 (to JW), the EU Innovative Medicines Initiative 2 Joint Undertaking (IMI2 JU), Grant/Award Number: No 115976 (PHAGO). PJ thanks the BIGS neuroscience and the University of Bonn for their support. PJ also thanks Lorenz Haase, Research department fundamental physics, Max Planck Institute for Radio Astronomy, Bonn, for his critical suggestions on the analysis done in this study. Authors thank the Microscopy Core Facility of the Medical Faculty at the University of Bonn for providing support and instrumentation funded by the Deutsche Forschungsgemeinschaft, Project Number: 388169927. Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft, Grant WA1477/6-6 (to JW), the EU Innovative Medicines Initiative 2 Joint Undertaking (IMI2 JU), Grant/Award Number: No 115976 (PHAGO). PJ thanks the BIGS neuroscience and the University of Bonn for their support. PJ also thanks Lorenz Haase, Research department fundamental physics, Max Planck Institute for Radio Astronomy, Bonn, for his critical suggestions on the analysis done in this study. Authors thank the Microscopy Core Facility of the Medical Faculty at the University of Bonn for providing support and instrumentation funded by the Deutsche Forschungsgemeinschaft, Project Number: 388169927. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1186/s40478-021-01263-x",
language = "English",
volume = "9",
journal = "Acta neuropathologica communications",
issn = "2051-5960",
number = "1",
}