330883 RESULTS
COMMENT These are intriguing findings. It is clear from animal and human studies that ApoE4 has a major effect on Aβ aggregation in the brain, via affecting Aβ clearance and the process of Aβ aggregation itself. ApoE may have a variety of other actions in the cen
COMMENT I daresay, "most intriguing" (referring to the famous Belgian Janssen twins). This could add weight to the Tomm40 implication in AD—but also to "cognitive ageing"? fred.vanleuven 0 A genome-wide association study implicates the APOE lo
COMMENT It is unfortunate that neurologists and psychiatrists with advanced training in dementia who face many diagnostically challenging cases cannot utilize amyloid PET in their clinical practice. Amyloid PET can be incredibly useful diagnostically and prognost
COMMENT There is strong evidence that ApoE interacts with β amyloid to affect its aggregation and clearance, and this may be a major component of ApoE’s role in AD. That said, a number of other potential mechanisms may be involved in ApoE’s contribution to AD, in
COMMENT The finding that ApoE4 carriers display Aβ-independent pathomechanisms is not really surprising. To give a few examples of Aβ-independent effects of ApoE4, the literature shows that ApoE4 carriers also have poor outcome following traumatic brain injury, a
COMMENT As foundries were the drivers of the industrial revolution, databases are the drivers of the information revolution. Some of these legacy databases provide details on the course of ALS for those patients eligible for clinical trials, and who were therefor
COMMENT This is a very important and extremely interesting work. I am glad to see the 8-angstrom-deep water-accessible cavity near the cytosolic side of the membrane. We saw this in our cryo-EM structure in 2008. We suspected, but didn't have evidence at tha
COMMENT This is certainly an absolutely fantastic breakthrough. For the very first time, we can see structural details of presenilin! Moreover, I am extremely pleased that many of the seminal findings on structure/function relationships made by numerous researche
COMMENT The crystal structure of an archaea homologue of presenilin (mmPSH), just published in Nature, represents a substantial advance in the structural field of membrane proteins that could shed light on the structural basis of the active site of the γ-secretas
COMMENT By Taisuke Tomita and Takeshi Iwatsubo Li and colleagues have provided the first crystal structure of an archaeal presenilin protein. As the authors mentioned, despite extensive years of efforts on eukaryotic presenilins, the crystal structure of PS has n
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 The paper by Li et al. is a real tour de force that offers the first atomic resolution information about the three-dimensional structure of presenilins. Multiple laboratories around the world attempted to crystallize presenilins previously but have not be
COMMENT The existence of such a hole was previously envisioned in our article, where we explained the hypothetical role of such a pore. mmanotas 0 Are γ-secretase and its associated Alzheimer's disease γ problems?
COMMENT The largest contributor to dementia's expansion is that, worldwide, people are living longer. When you have four times the number of people in the older age groups (projected for the middle of the century), you automatically will have four times the
COMMENT The question remains whether the true information from the recently failed clinical trials of ceftriaxone and olesoxime lies in the fact that the overall clinical care of patients with ALS has significantly altered, at this point in time, disease trajecto
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