Journal Article

DZNE-2021-01357

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Differential interaction with TREM2 modulates microglial uptake of modified Aβ species.

Joshi, P. ; Riffel, F. ; Satoh, K. ; Enomoto, M. ; Qamar, S. ; Scheiblich, H.DZNE* ; Villacampa, N.DZNE* ; Kumar, S. ; Theil, S. ; Parhizkar, S. ; Haass, C.DZNE* ; Heneka, M.DZNE* ; Fraser, P. E. ; St George-Hyslop, P. ; Walter, J.

2021
Wiley-Liss Bognor Regis [u.a.]

This record in other databases:    

Please use a persistent id in citations: doi:10.1002/glia.24077

Abstract: Rare coding variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2) confer an increased risk for Alzheimer's disease (AD) characterized by the progressive accumulation of aggregated forms of amyloid β peptides (Aβ). Aβ peptides are generated by proteolytic processing of the amyloid precursor protein (APP). Heterogeneity in proteolytic cleavages and additional post-translational modifications result in the production of several distinct Aβ variants that could differ in their aggregation behavior and toxic properties. Here, we sought to assess whether post-translational modifications of Aβ affect the interaction with TREM2. Biophysical and biochemical methods revealed that TREM2 preferentially interacts with oligomeric Aβ, and that phosphorylation of Aβ increases this interaction. Phosphorylation of Aβ also affected the TREM2 dependent interaction and phagocytosis by primary microglia and in APP transgenic mouse models. Thus, TREM2 function is important for sensing phosphorylated Aβ variants in distinct aggregation states and reduces the accumulation and deposition of these toxic Aβ species in preclinical models of Alzheimer's disease.

Keyword(s): Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Amyloid beta-Protein Precursor: genetics (MeSH) ; Amyloid beta-Protein Precursor: metabolism (MeSH) ; Animals (MeSH) ; Disease Models, Animal (MeSH) ; Membrane Glycoproteins: genetics (MeSH) ; Membrane Glycoproteins: metabolism (MeSH) ; Mice (MeSH) ; Mice, Transgenic (MeSH) ; Microglia: metabolism (MeSH) ; Receptors, Immunologic: genetics (MeSH) ; Receptors, Immunologic: metabolism (MeSH) ; Alzheimer's disease ; FTD mutation ; TREM2 ; amyloid β ; phosphorylation ; post-translational modification

---

Contributing Institute(s):

1. Interventional Trials and Biomarkers in Neurodegenerative Diseases (Biomarker)
2. Neuroinflammation, Biomarker (AG Heneka)
3. Molecular Neurodegeneration (AG Haass)
4. Technology Transfer and Industry Collaborations Unit (Tech Transfer)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)
3. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2021

---

Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---