11505 RESULTS
COMMENT Homeostatic Control: Relevance to Alzheimer Disease Larsen and Clarke highlight that endogenous homeostatic control over energetics and endogenous antioxidant defenses make cells and organisms better adapted to survival than exogenous intervention. These
COMMENT I find the study interesting because our work suggests that SIR2 will be a universal regulator of aging (definitely in yeast and worms) and we recently found that it functions as a negative regulator of p53 in mammalian cells. My hunch is that this is onl
COMMENT Reply by Akihiko Takashima Regarding Peter Davies' comment, I would like to reply. We
COMMENT The Takashima mice are remarkable, as they appear to express high levels of the mutant tau protein in only a very few cells in the brain: that is, in some of the pyramidal cells of the hippocampus. Apparently the transgene is expressed at only very low le
COMMENT This is one of the few studies that have longitudinally explored the relation between leisure activities and dementia. The authors carefully tested the hypothesis that leisure activities contribute to the reserve against dementia by reserving a set of ski
COMMENT This report is relevant both from the perspectives of pathogenesis (i.e., does chaperone activity alter susceptibility to PD ?) and potential avenue for therapeutic intervention (i.e., could increasing chaperone Hsp70 activity confer neuroprotection of af
COMMENT These results are an important confirmation of findings previously reported. The authors were appropriately cautious in pointing out potential limitations to the interpretation of this study, including a potential ability of more highly educated people to
COMMENT Despite intensive study the functions of APP are unknown, however an increasing number of experiments are identifying functions of APP. This paper is interesting because it identifies a function that appears to be dependent on APP which, if true, would be
COMMENT This careful study rigorously tests a creative concept. We have also detected BACE and APP, though not PS-1, in the same subcellular compartment in AD neurons. That APP, BACE and PS1 are colocalized at the same subcellular site in axons is intriguing and
COMMENT Dr. Gandy proposes that estradiol/testosterone activate ERK, so that hormone withdrawal would decrease ERK, a reasonable scheme since many hormone-regulated pathways are reduced in aging. But Aβ is overly produced in the same period and whole world is dev
COMMENT Reply by Sam Gandy We have no data on gonadotrophins and either Abeta metabolism or Alzheimer risk, though it should be relatively straightforward to obtain. In general, I would suspect that the neurobiology of hormone withdrawal following decades of thei
COMMENT Reply by Sam Gandy The mechanism(s) by which estradiol/testosterone control(s) Aβ levels are yet to be definitively elucidated. Our working model is that estradiol/testosterone activate ERK (MAPK), a signalling pathway well-known to be estrogen-sensitive
COMMENT Hormone reduction (gonadal, estrogen, testosterone) is one of the most salient changes in aging (amid energy and growth factor decline, metal imbalance, free radicals, etc.). So it is expected and has been shown to contribute to (though may not be solely
COMMENT Participants in the forum may be aware that there has been an ongoing dialogue between myself and Dr. Gandy on the role of gonadal hormones in the etiology of Alzheimer's disease and this discussion has been recently published as letters in JAMA. Whi
COMMENT Aβ-degrading enzymes—many candidates, but few fit the bill This comment extends the news report
