32 RESULTS
COMMENT This is an intriguing study highlighting the importance of TREM2-dependent microglial activity in protecting against neurotoxic pathology associated with β-amyloidosis. Unique to this study is their use of PS2APP mice to examine sex- and age-dependent Tre
COMMENT The role of microglia in amyloid generation/removal appears to be very complex. The authors now present clear data that the presence of microglia is required to allow amyloid plaque deposition. We favor their argument that microglia may secrete factors th
COMMENT We want to clarify an important point. The goal of our study was not to finally determine if sTREM2 or full-length TREM2 exert a protective function, or which variant needs to be therapeutically modified. Rather, we wanted to find out whether TREM2 is pro
COMMENT This paper reproduces findings in human iPSC-derived neurons that others made decades ago in much simpler cell systems. These cell lines are therefore a nice and important resource for future research, but I would have expected a balanced discussion and
COMMENT I find it very interesting that sTREM2 can promote functions that we thought are associated with membrane bound full-length TREM2. This indeed makes therapeutic modulation of TREM2 even more tricky, since we now have not only to consider “overactivation”
COMMENT This is a study the entire field has been waiting for, for a long time. After the initial finding that BACE1 is required for myelination via neuregulin 1 processing back in 2006 (!) (Hu et al., 2006; Willem et al., 2006), a number of other substrate-relat
COMMENT Recent advances in the methodology of deriving macrophages and microglia-like cells from induced pluripotent stem cells (iPSCs) has opened up new opportunities to functionally characterize the effects of disease-associated variants (e.g. TREM2, CD33 …) us
COMMENT Since it is notoriously difficult to investigate microglial function in human brains, and so-called microglial cell lines do not faithfully reproduce the characteristics of microglia isolated from brain (Butovsky et al., 2014), human microglia are an extr
COMMENT This is a very important paper. Colonna and colleagues provide clear evidence that the most relevant AD-associated variant (TREM2 p.R47H) causes a partial loss of function. The authors show this by an elegant approach. They rescue TREM2 KO phenotypes by t
COMMENT Although there were several attempts to determine the age and turnover of microglia in the past, this is what the field has been waiting for for a long time! Now, we know it: Mice are basically born not only with most, if not all, of their neurons and oli
COMMENT In this extremely exciting paper, the Colonna lab shows that TREM2-deficient, dysfunctional microglia can be therapeutically modulated to regain their original defense mechanisms. Ulland and colleagues show this by restoring energy supply via stimulation
COMMENT This is exciting news—more and more evidence is now provided for a causative role of microglial dysfunction in Alzheimer's disease and other neurodegenerative disorders. Strikingly, this paper not only confirms an AD-associated TREM2 variant in a gen
COMMENT The interesting study of Cooper-Knock et al. highlights the importance of a TREM2-dependent, potentially protective, microglia function in the pathogenesis of ALS. This also supports a general function of TREM2 and microglia as modifiers for several disti
COMMENT As a postdoc in Dennis Selkoe's lab, and later as a group leader back in Germany, I had the pleasure and honor to collaborate on several major research projects with Dale. Dale was one of the greatest and most visionary scientists I ever collaborated
COMMENT A perfect example for sharing biological samples is DIAN. This is exactly how biological samples from clinical cohorts should be made available to the research community with the goal of performing the best science. This is clearly in the interest of the
