8066 RESULTS
COMMENT Finding a safe therapeutic window in which the dose range of BACE1 inhibitors is adjusted between tolerable mechanism-based toxic effects and Aβ reduction will be crucial to achieve a safe AD therapy. Although Bace1null mice abolish amyloid generation, ...
COMMENT This is a large, well-done study of 719 patients overall and 254 with suspected non-AD disorders from a diverse group of three sites around the world. The tau-PET data is supplemented by amyloid-PET data. The sensitivity/specificity (90/91 percent and 97 ...
COMMENT This excellent and carefully conducted study finally demonstrates that most of the phenotypes observed so far in BACE1-deficient mice are of developmental origin and may not be a cause of concern for the BACE inhibitors tested in the clinic. Yet, the ...
COMMENT We appreciate Dr. Kukull’s thoughtful comments. He identifies the importance of randomization to establish comparability of treatment groups in clinical trials. We have no evidence that the treatment groups in this RCT differed with respect to any ...
COMMENT I appreciate the interesting points in two separate comments by Drs. Tanaka and Ozdinler. The published work of Tanaka’s group on the role of mutant PFN1 disorganizing TDP-43 is of great interest and is consistent with the evidence that we presented that ...
COMMENT We are grateful for Dr. Hendrie’s kind words and reasonable caution. We agree that engagement in cognitive, physical, and/or social activities needs to be a lifetime process. We inculcated that message by having participants develop activity goals that ...
COMMENT We think that the papers are very nice! Eguchi et al. confirm all our recently published findings and they observe an increase in Rab10 phosphorylation upon lysosomal activation, which is very intriguing. This is the very first time that we have seen a ...
COMMENT There is a general consensus amongst researchers in aging that engagement in its various forms, exercise, cognitive, and social, are major factors in preserving health, including cognitive health and well-being in the elderly. However this concept has ...
COMMENT For a randomized controlled trial, one expects that a variety of important risk factors or determinants of cognitive decline or its measurement (APOE, education, existing vascular and neurodegenerative pathology) would be distributed equally, if ...
COMMENT Both Bae et al. and Eguchi et al. show LRRK2 functioning in the endocytic recycling pathway, which is consistent with an earlier study by Mark Cookson’s group showing that LRRK2 interacts with Rab7L1—a protein involved in endosomal recycling (Beilina et ...
COMMENT Two recent studies report on the role of LRRK2 in altering endolysosomal structure/function and lysosomal secretion, albeit coming to different conclusions. Eguchi et al. used various tissue culture cell lines treated with chloroquine, a lysosomotropic ...
COMMENT This paper builds on work from the same lab showing seasonal variation in brain gene expression, and the data are in keeping with other studies linking seasonality to cognition (Meyer et al., 2016). These findings are very interesting and important, as ...
COMMENT This is a fascinating paper showing seasonal differences in cognition and related biological measures. The authors show that cognitive performance peaks around the time of the fall equinox. The impact of seasonal variation on cognition is large, ...
COMMENT Recent advances in the methodology of deriving macrophages and microglia-like cells from induced pluripotent stem cells (iPSCs) has opened up new opportunities to functionally characterize the effects of disease-associated variants (e.g. TREM2, CD33 …) ...
COMMENT Xiang et al. report altered splicing of mouse TREM2 that is dependent upon the presence of the R47H mutation that was introduced into mice by three different groups (Christian Haas and colleagues, Bruce Lamb/Gary Landreth, and the MODEL-AD Consortium). ...
