8 RESULTS
COMMENT The paper is interesting and potentially important. That retromer-regulated trafficking is important in tauopathies, including Alzheimer’s disease, is well-established (e.g., Mishra et al., 2023). However, the direct binding of tau to SORL1 is a new findi
COMMENT I think most thoughtful people in the field have wished for better antibodies for some time. This work will make it clear how urgent that is. The question is whether it’s possible to get them. Structural biologists have often been suspicious of ‘conformat
COMMENT In our 2014 paper, Scott Small’s lab and ours collaborated to show that R33 (and a related compound, R55, which I think some companies call TPT-260) stabilized retromer in vitro and also increased retromer protein levels in neurons in culture. Treatment w
COMMENT It's important to remember not only that the most compelling evidence for Aβ as a driver of Alzheimer's disease is, as Dennis mentions, the human genetic data, but that this is most relevant to the genetic form of AD. The driver(s) of the more c
COMMENT The study is well-done, which is not surprising considering who did it. The authors are quite properly cautious about the long-term therapeutic implications since their molecule is a long way from being a drug; nevertheless, many projects have begun this
COMMENT See also Jessica Young's recent paper, which also shows tau effects in AD patient-derived neurons independent of APP (Young et al., 2018). As for a small molecule corrector of ApoE4 deficits, yes, that is one approach, but I would argue that a more p
COMMENT This duet of papers represents the swan song of one of the deepest thinkers into the fundamental biology of neurodegeneration, our recently departed friend Sue Lindquist, who sadly died a few months ago. The papers illustrate the magnificent creativeness
COMMENT The work seems carefully done, and the results are clearly presented. I also think it represents an important attempt to get at a central problem in neuodegenerative diseases in general (and ALS in particular): the issue of selective vulnerability. Take t
