36 RESULTS
COMMENT This excellent and carefully conducted study finally demonstrates that most of the phenotypes observed so far in BACE1-deficient mice are of developmental origin and may not be a cause of concern for the BACE inhibitors tested in the clinic. Yet, the auth
COMMENT This is an interesting paper adding to our understanding of physiological BACE1 functions. It demonstrates that BACE1 controls neuronal differentiation. This study is different from a previous paper by Riqiang Yan (Hu et al., 2013) in that it now analyzes
COMMENT This is indeed bad news. Together with other recently terminated trials, it emphasizes the view that BACE inhibitors are unlikely to be effective when used to treat symptomatic individuals. They are likely to be more effective when used as a preventive ap
COMMENT This is a very interesting study that provides several important advances and insights for the field. It is particularly intriguing to see that BACE1 inhibition not only reduces plaque growth, but may even shrink existing plaques. If it also happens in pa
COMMENT The termination of this trial is sad news for the Alzheimer patients, but does not surprise me. The termination simply shows that BACE inhibitors need to be given early—as a secondary prevention—to be successful. Thus, clinical trials with BACE inhibitors
COMMENT This study is an important contribution to the validation of the amyloid hypothesis in vivo. Since the identification of this Icelandic mutation, it has been debated whether the apparently protective effect of the mutation is primarily due to its lowered
COMMENT This is sad news for Alzheimer’s patients and their families. Scientifically, it is not surprising that verubecestat did not have a positive effect, given that the target patient population was already at an advanced disease stage. The lack of a positive
COMMENT This is an interesting paper. I am looking forward to seeing more mechanistic characterization in the future, in particular using primary neurons and endogenous APP, but also regarding the mechanistic basis of the differential effect on different BACE sub
COMMENT It is great for the whole field that the Merck group publishes their preclinical and Phase I data. The results look very promising for the ongoing Phase 3 trials. A very interesting finding is that a potential side effect—the fur depigmentation—only occur
COMMENT This is an interesting paper, which follows up on an earlier paper in PNAS in 2010 from the same group. Randy has been following the endocytic connection in AD for many years and has published very well on the topic. The paper provides additional evidence
COMMENT I am particularly intrigued to see that the BACE1 inhibitor still has such a strong effect in old mice where amyloid pathology is already heavily visible. Currently, we think that amyloid-lowering drugs may have their strongest effect in a preventive but
COMMENT Although such a function may seem extremely unusual, it fits with a previous study from the same group and with increasing reports about non-proteolytic functions of other proteases, such as a transcription factor function of MMP-12 in antiviral immunity
COMMENT This is an interesting paper, which fits well with earlier findings reported from Phil Wong’s lab in BACE1-deficient mice (Savonenko et al., 2008). After Carmen Birchmeier’s report last year (Cheret et al., 2013), this is now another story demonstrating t
COMMENT I really like this paper. It shows that a mild overexpression of human BACE1 in mice can induce pathological changes similar to those seen in a human AD brain. It is amazing that the changes happen so early (behavioral and memory changes after a few month
COMMENT This is a scientifically exciting story that is genetically well controlled, including the conditional knockout of the substrate neuregulin 1. The paper adds muscle spindle formation to the growing list of BACE1 in-vivo functions. Another important aspect
