TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis

By G. Kleinberger, Y. Yamanishi, M. Suárez‐Calvet, Eva Czirr, E. Lohmann, Elise Cuyvers, H. Struyfs, Nadine Pettkus, Andrea Wenninger-Weinzierl, F. Mazaheri and 23 more. Science Translational Medicine, 2014

750 citations recorded by the source corpus.

Subfields: Immunology, Neurology

View Paper: https://www.semanticscholar.org/paper/104e4a2ceb2d71f1e796fcf0a799d03e103b54c9

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. D. Holtzman
2. O. Butovsky
3. M. Colonna
4. Morgan Sheng
5. M. Cella
6. R. Ransohoff
7. Berislav Zlokovic
8. J. Long

In Neurology

1. D. Holtzman
2. O. Butovsky
3. D. Selkoe
4. M. Colonna
5. John Hardy
6. R. Ransohoff
7. J. Long
8. Berislav Zlokovic

Citations in the corpus

• TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models (2015, background): “TREM2 variants such as the missense mutation Q33X (R. Guerreiro et al., 2013) and the FTD-related variants T66M and Y38C which impair protein maturation (Kleinberger et al., 2014), almost certainly impair TREM2 function.”
• Microglia in Alzheimer’s disease (2018, background): “Homozygous null mutations in TREM2 cause Nasu–Hakola disease, characterized by early onset neurodegeneration (including white matter lesions) and bone abnormalities (Paloneva et al., 2002; Klünemann et al., 2005).”
• TREM2 lipid sensing sustains microglia response in an Alzheimer’s disease model (2015, positive): “…homozygous for rare mutations that impair expression of either TREM2 or DAP12, develop lethal forms of progressive, early-onset dementia such as Nasu-Hakola disease (NHD) and frontotemporal dementia (Guerreiro et al., 2013a; Guerreiro et al., 2013c; Kleinberger et al., 2014; Paloneva et al., 2002).”
• The amyloid hypothesis of Alzheimer's disease at 25 years (2016, background): “However, the biology of TREM2, a Type 1 single-transmembrane receptor which is principally but not exclusively expressed in microglia and undergoes ADAM/ c-secretase processing (Wunderlich et al, 2013; Kleinberger et al, 2014), is incompletely understood [reviewed in (Lue et al, 2015)].”