43 RESULTS
COMMENT These are fascinating studies. They remind us there is a lot we do not know about the biology of AD. They reinforce that we need to solve the mystery of how Aβ talks to tau. They also show that kinetics matter. There has been some literature (e.g. Wogulis
COMMENT Chad was a great friend and colleague. I first met him when I was a young faculty member at Mayo Clinic in Florida, and Chad was a postdoctoral fellow. He was later promoted to a research track assistant professor and I soon thereafter became his chair. L
COMMENT Our consortium RNAseq data is available at synapse.org, along with other groups’ data. This data and RNAseq data from Ben Barres and colleagues at Stanford is consistent and pretty unequivocal. In humans, Lag3 RNA levels are ~500- to 1000-fold lower in th
COMMENT comments here, I am saddened to hear this news. In the early days of Athena, there was a great but yet
COMMENT These data look quite interesting and the binding rather compelling. But I would caution that LAG3 is an immune checkpoint molecule whose expression in mice is thought to be largely restricted to T-cells and, in the brain, largely microglial cells. In hum
COMMENT Bart De Strooper’s essay in Cell is a thoughtful evaluation of a “failed” γ-secretase inhibitor (GSI) trial with semagacestat. I agree that the clinical trials with this compound could have been conducted in ways that would provide more guidance for futur
COMMENT It is likely that innate immune activation can have positive or negative effects on proteostasis and behavioral and neurodegenerative phenotypes. That balance between positive and negative effects would contextually depend on the nature, timing, duration,
COMMENT My take is that this is fundamentally sound but that some GSMs clearly interact with substrate. Ultimately, I think the truth will be that there will be flavors of GSMs that interact with substrate, substrate and presenilin/γ-secretase, and combinations o
COMMENT I remain agnostic as to what studies of in vitro toxicity tell us about pathogenic mechanisms in Alzheimer's disease. I think the data is unequivocal that dumping protein aggregates on neurons in culture is harmful, but it has been challenging to pro
COMMENT a few issues that I see as most important. Obviously, the following comments may be tempered somewhat by
COMMENT With respect to Dr. Davies's comments, I think first and foremost we have to consider the
COMMENT I think we in this field have to be careful with overinterpreting phenomena in our APP mouse models. Transgenic mouse models expressing AD-associated mutant forms of the amyloid-β precursor protein (APP), or both mutant APP and mutant presenilin-1 (PS1),
COMMENT This is a very interesting story, but assumes a widespread underlying premise that is incorrect. Namely that dopaminergic substantia nigra neurons are selectivley damaged in Parkinson Disease. It is true that dopaminergic SN neurons are selectively reduce
COMMENT It is important to clarify the statement "Flurbiprofen is the only approved NSAID still in the running for an AD therapy, though the one discussed here is a version trademarked by Myriad Pharmaceuticals. " The drug under investigation is R-flurb
COMMENT The recent manuscript by Zhou et al. clearly shows that CD147 co-purifies with the γ-secretase complex. However, the claim that it is a novel regulatory subunit of the complex is likely to be debated. CD147 is a type 1 membrane protein that is in the IgG
