33 RESULTS
COMMENT I was deeply saddened to hear that Peter had passed recently. I had deep respect for Peter as a scientist and a colleague. Publically, Peter kept faith as a “tauist” and championed its role in AD and related disorders. Especially in the early 1990s, this ...
COMMENT This manuscript by the Heneka lab dissects the influence of inflammasome activation on tau pathology in a mouse model of tauopathy. The notion that exacerbated inflammatory responses can accelerate tau pathology ties in with previous reports indicating ...
COMMENT In response to Kariem Ezzat, we'd like to note that, having looked at thousands of Aβ IHCs, we would suggest that the "plaques" shown look pretty compact and not diffuse. This is what prompted our original critique. As biochemical data was ...
COMMENT This is an intriguing study. The ex-vivo “test tube” studies are quite convincing that HSV and other virus particles can nucleate Aβ fibril formation. However, we find the report in Figure 7 that inoculation of 3-month-old 5XFAD mice with HSV1 ...
COMMENT Was this the right drug at the wrong time? Or another "wrong" drug? (See Golde et al., 2018). This is a critical question for the field to answer. There is evidence that this antibody reduces the amyloid PET ligand signal in many trial ...
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. ...
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 ...
COMMENT My heart goes out to Dale's family, friends, and colleagues. Like all of the others posting comments here, I am saddened to hear this news. In the early days of Athena, there was a great but yet friendly competition between Athena, the Younkin lab, ...
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 ...
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 ...
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 ...
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 ...
COMMENT The recent follow-up to the AN1792 study by Holmes et al. is a thought-provoking study that reinforces but certainly does not prove speculation by many in the field, including myself (Golde, 2006; Golde, 2003), that therapeutic targeting of Aβ may have ...
