32 RESULTS
COMMENT How do young investigators and newcomers in the AD field identify the most relevant findings when, every day, a large number of papers is published? They do not even have the time to read all of the new ones, much less easily judge which of these publicat
COMMENT We and others have consistently shown that the LOAD-associated TREM2 H157Y variant—which occurs right at TREM2’s ADAM10/17 cleavage site—increases shedding of sTREM2. It therefore decreases TREM2 signaling and function, because signaling-competent cell su
COMMENT This manuscript by the Ryskeldi-Falcon lab clarifies several important issues. It is clear now that TDP-43 forms amyloid fibers in FTLD Type A and Type B—and, as in other neurodegenerative diseases, these fibers show distinct structures and are therefore
COMMENT I met Yasuo more than three decades ago when I was still working in Boston. He was one of the most thoughtful and “quiet” scientists I ever met. With Yasuo’s passing, not only a brilliant scientist, but also a leader in the field, has left us. I admired Y
COMMENT This may be an extremely important discovery. The findings of the Selkoe lab suggest that they finally identified the neurotoxic Aβ assembly that everybody has been looking for, for decades (Haass and Selkoe, 2007). These are not small soluble oligomers,
COMMENT Back in 2014 we proposed for the first time that increasing cell-autonomous TREM2 signaling in microglia may be exploited to modulate their protective activities (Kleinberger et al., 2014). In a proof-of-principle study, we inhibited shedding to increase
COMMENT I am speechless about these allegations. This damages the reputation of the oligomer research field, where much good work is being done. Regarding Aβ56*, we were skeptical about the data from the beginning, and our lab never started a project on it. chris
COMMENT What a surprise! Nowadays, one would assume that rather simple pathological abnormalities, such as intracellular amyloid filaments, should have been seen by neuropathologists for a long time. Not so. Suddenly, three independent publications pop up and rep
COMMENT I have been waiting for such an analysis for a long time. This is indeed a very important story, which finally relates high Aβ38 levels to reduced cognitive decline in two independent cohorts, although the mechanism remains unclear. Is it a reduction of l
COMMENT As already pointed out by David Holtzmann, cross-sectional correlations between biomarkers in an observational study do not imply causation. Moreover, the claim that microglial activation together with amyloid accumulation is a driver of tau spreading sho
COMMENT This is a mouse model for amyloidosis, which, finally, is freely available for the entire research community. This is a big issue, considering that many experiments were blocked or slowed due to legal issues with mouse models. I think this is a great sign
COMMENT In the current study the Colonna lab describes very similar properties of a new TREM2 agonistic antibody as in their previous paper using the Alector antibody AL002c which binds to the stalk region of TREM2 (Wang et al., 2020). To us, it looks like hT2AB
COMMENT We read this article with great interest. This work provides a convincing confirmation of the value of TREM2 agonist antibodies in mouse models of AD while providing new details on the impact of these antibodies on microglial state through single-cell RNA
COMMENT This paper suggests a dual role of TREM2 during disease evolution. Early on TREM2 risk variants increase Aβ toxicity and promote its spreading (see also Parhizkar et al., 2019). Similarly, TREM2 risk variants appear to promote tau spreading in early phase
COMMENT This is a very important paper, because it supports the idea to therapeutically modulate TREM2 functions in microglia. Andreone and colleagues independently support this approach by demonstrating shared LOF phenotypes upon TREM2 or PLCγ2 knockout. This su
