Journal Article

DZNE-2020-03779

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis.

Kleinberger, G. ; Yamanishi, Y. ; Suárez-Calvet, M. ; Czirr, E. ; Lohmann, E.DZNE* ; Cuyvers, E. ; Struyfs, H. ; Pettkus, N. ; Wenninger-Weinzierl, A.DZNE* ; Mazaheri, F.DZNE* ; Tahirovic, S.DZNE* ; Lleó, A. ; Alcolea, D. ; Fortea, J. ; Willem, M. ; Lammich, S. ; Molinuevo, J. L. ; Sánchez-Valle, R. ; Antonell, A. ; Ramirez, A. ; Heneka, M.DZNE* ; Sleegers, K. ; van der Zee, J. ; Martin, J.-J. ; Engelborghs, S. ; Demirtas-Tatlidede, A. ; Zetterberg, H. ; Van Broeckhoven, C. ; Gurvit, H. ; Wyss-Coray, T. ; Hardy, J. ; Colonna, M. ; Haass, C. (Last author)DZNE*

2014
AAAS Washington, DC

This record in other databases:    

Please use a persistent id in citations: doi:10.1126/scitranslmed.3009093

Abstract: Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to Nasu-Hakola disease, Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and FTD-like syndrome without bone involvement. TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis. Whether and how TREM2 missense mutations affect TREM2 function is unclear. We report that missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells. As a consequence of reduced shedding, TREM2 is virtually absent in the cerebrospinal fluid (CSF) and plasma of a patient with FTD-like syndrome. A decrease in soluble TREM2 was also observed in the CSF of patients with AD and FTD, further suggesting that reduced TREM2 function may contribute to increased risk for two neurodegenerative disorders.

Keyword(s): Alzheimer Disease: genetics (MeSH) ; Biological Transport: genetics (MeSH) ; Biological Transport: physiology (MeSH) ; Cell Line (MeSH) ; Cells, Cultured (MeSH) ; Enzyme-Linked Immunosorbent Assay (MeSH) ; Frontotemporal Dementia: genetics (MeSH) ; Humans (MeSH) ; Membrane Glycoproteins: genetics (MeSH) ; Mutation (MeSH) ; Neurodegenerative Diseases: genetics (MeSH) ; Phagocytosis: genetics (MeSH) ; Phagocytosis: physiology (MeSH) ; Receptors, Immunologic: genetics (MeSH) ; Membrane Glycoproteins ; Receptors, Immunologic ; TREM2 protein, human

---

Contributing Institute(s):

1. Parkinson Genetics (AG Gasser 1)
2. ALS, FTLD and Zebrafish models (AG Haass old)
3. Ex vivo models (AG Tahirovic)
4. Neuroinflammation, Biomarker (AG Heneka2)

Research Program(s):

1. 345 - Population Studies and Genetics (POF3-345) (POF3-345)
2. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)
3. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2014

---

Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; IF >= 15 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---