TY  - JOUR
AU  - Joshi, Pranav
AU  - Riffel, Florian
AU  - Kumar, Sathish
AU  - Villacampa, Nàdia
AU  - Theil, Sandra
AU  - Parhizkar, Samira
AU  - Haass, Christian
AU  - Colonna, Marco
AU  - Heneka, Michael
AU  - Arzberger, Thomas
AU  - Herms, Jochen
AU  - Walter, Jochen
TI  - TREM2 modulates differential deposition of modified and non-modified Aβ species in extracellular plaques and intraneuronal deposits.
JO  - Acta Neuropathologica Communications
VL  - 9
IS  - 1
SN  - 2051-5960
CY  - London
PB  - Biomed Central
M1  - DZNE-2021-01343
SP  - 168
PY  - 2021
N1  - CC BY
AB  - Progressive accumulation of Amyloid-β (Aβ) deposits in the brain is a characteristic neuropathological hallmark of Alzheimer'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.
KW  - Aged
KW  - Aged, 80 and over
KW  - Alzheimer Disease: pathology
KW  - Amyloid beta-Peptides: chemistry
KW  - Amyloid beta-Peptides: metabolism
KW  - Animals
KW  - Female
KW  - Humans
KW  - Male
KW  - Membrane Glycoproteins: genetics
KW  - Membrane Glycoproteins: metabolism
KW  - Mice
KW  - Neurons: pathology
KW  - Plaque, Amyloid: chemistry
KW  - Plaque, Amyloid: pathology
KW  - Receptors, Immunologic: genetics
KW  - Receptors, Immunologic: metabolism
KW  - Aβ (Other)
KW  - Intraneuronal (Other)
KW  - Microglia (Other)
KW  - Post-translational modification (Other)
KW  - TREM2 (Other)
KW  - Vascular deposits (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34663480
C2  - pmc:PMC8522217
DO  - DOI:10.1186/s40478-021-01263-x
UR  - https://pub.dzne.de/record/162686
ER  -