219 RESULTS
COMMENT No adverse side effect of β-secretase inhibitors is indeed good news, but something has been bugging me since I read the news. We can attribute the absence of β-secretase inhibitors’ side effect to an alternative cleavage by α-secretase. The α-secretase c
COMMENT It was 2003 when Takeshi Iwatsubo and I tried to visit Dale in San Francisco after the Society for Neuroscience meeting in San Diego. Because of heavy fog, the direct flight was cancelled, so we needed several hours to reach San Francisco via fragmented f
COMMENT We would like to emphasize that the APP knock-in mice do not display any tau pathology or neurodegeneration. This suggests that Aβ pathology might account, at least in part, for cognitive dysfunction in AD via disturbance of neuronal activities, because w
COMMENT I appreciate the comments from Li-Huei Tsai and Karen Ashe. It is always good to see the same
COMMENT Scientists who have experience isolating Aβ from human brains may find the data shown in Figure 1 puzzling. Our lab has found Aβ deposits in human brain to be as hard as rocks. Because Aβ deposits resist such detergents as SDS, we usually depend on formic
COMMENT This is an innovative work, which, at least in part, explains the region-specific vulnerability of brain to neurodegenerative processes. The presented scheme is beautiful. I do however have a concern. Systems biology relies on the presumption that all the
COMMENT Preclinical AD starts more than two decades before the disease onset. This indicates that asymptomatic patients may keep taking medication for many years, almost until the end of life. The medication therefore must be safe for a long time, and I would say
COMMENT Even from the view of the Far East, Brexit is sad, like a divorce hurting the younger generations. The most threatening is over-reaction. The exchange rate of the British pound against the Japanese yen is almost half of what it was one year ago. This mean
COMMENT I tend to agree with David Holtzman. One thing unclear to me is why the authors did not distinguish between ApoE4 carriers and non-carriers in their mathematical modeling. This is because ApoE4 genotype is an independent risk factor for vascular dysfuncti
COMMENT If the quantity of PS2 is much smaller than that of PS1 throughout development and aging, this will explain essentially every question about the difference between PS1 and PS2, and differential localization of PS2 may then be less important. Again, I urge
COMMENT A group led by Wim Annaert appears to have provided an answer to the question, “Why is the number of the pathogenic presenilin (PS) 2 mutations much smaller than that of PS1 mutations?” The authors demonstrate that PS2 is more tightly associated with acid
COMMENT Although I did not attend the Zilkha Symposium, I would like point the audience's attention to a classic study by Yu-Min Kuo and Alex Roher, whose title was “Water-soluble Aβ (N-40, N-42) Oligomers in Normal and Alzheimer Disease Brains" (Kuo &a
COMMENT Finally, I have one comment on the threonine 43 being hydrophilic. The free amino acid and the amino acid
COMMENT The cellular phase, defined by De Strooper and Karran, appears to largely represent intracellular and intercellular interactions responsible for AD development. They probably involve both gain of toxic functions and loss of normal functions. In my underst
COMMENT First of all, I would like to praise the hard work of Roy and other authors. By definition, however, early AD is the clinical condition that arises after MCI, where tauopathy and neurodegeneration had already started. So the models that the authors used i
