Journal Article

DZNE-2021-01343

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png TREM2 modulates differential deposition of modified and non-modified Aβ species in extracellular plaques and intraneuronal deposits.

Joshi, P. ; Riffel, F. ; Kumar, S. ; Villacampa, N.DZNE* ; Theil, S. ; Parhizkar, S. ; Haass, C.DZNE* ; Colonna, M. ; Heneka, M.DZNE* ; Arzberger, T.DZNE* ; Herms, J.DZNE* ; Walter, J.

2021
Biomed Central London

This record in other databases:    

Please use a persistent id in citations: doi:10.1186/s40478-021-01263-x

Abstract: 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.

Keyword(s): Aged (MeSH) ; Aged, 80 and over (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Amyloid beta-Peptides: chemistry (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Animals (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Membrane Glycoproteins: genetics (MeSH) ; Membrane Glycoproteins: metabolism (MeSH) ; Mice (MeSH) ; Neurons: pathology (MeSH) ; Plaque, Amyloid: chemistry (MeSH) ; Plaque, Amyloid: pathology (MeSH) ; Receptors, Immunologic: genetics (MeSH) ; Receptors, Immunologic: metabolism (MeSH) ; Aβ ; Intraneuronal ; Microglia ; Post-translational modification ; TREM2 ; Vascular deposits

Note: CC BY

---

Contributing Institute(s):

1. Molecular Neurodegeneration (AG Haass)
2. Interventional Trials and Biomarkers in Neurodegenerative Diseases (Biomarker)
3. Translational Brain Research (AG Herms)
4. Neuropathology / Brainbank (Neuropathology / Brainbank)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2021

---

Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---