Troy Rohn on Tackling Alzheimer’s from the Outside In

COMMENT thought it was one of the best presentations I heard. In regard to the comments by Thomas Bayer, who

David Holtzman on ABCA1 Links Cholesterol and ApoE, But It May Not Be a Risk Factor for AD

COMMENT ABCA1 has been shown to be critical outside the brain for effluxing phospholipid and cholesterol from cells onto HDL. In the periphery, ApoAI is the main apolipoprotein in HDL. The absence of ABCA1 function results in Tangier's disease in which plasm

Rudy Tanzi on ABCA1 Links Cholesterol and ApoE, But It May Not Be a Risk Factor for AD

COMMENT After ApoE, which has an unusually large effect size as a late-onset AD gene, the remaining AD genes would be expected to have more modest to moderate effect sizes. Thus, one really needs to routinely use at least a thousand or so uniformly ascertained su

James Nicoll on Philadelphia: Can a Shrinking Brain Be Good for You?

COMMENT The brain volume changes in patients who were immunized and developed antibodies is interesting, but perhaps not so surprising in retrospect when the information available from the neuropathology is taken into account. You might predict (1) an initial tra

Thomas Bayer on Tackling Alzheimer’s from the Outside In

COMMENT The paper by Oddo et al published in Neuron 2004 is most interesting. Together with the earlier reports (Oddo et al., 2003a; Oddo et al., 2003b) the authors describe a “missing link” between Aβ-amyloid and Tau pathology in an animal model for Alzheimer�

David Stern on Promoter Bashing—Mitochondrial Ones Damaged in AD Brain

COMMENT A possible role for abnormal mitochondrial biology in the pathogenesis of Alzheimer’s disease (AD) has been an omnipresent theme over the last decades. Regional hypometabolism, documented by positron emission tomography and abnormalities in mitochondrial

John Trojanowski on Tackling Alzheimer’s from the Outside In

COMMENT The paper from the LaFerla lab is most interesting, and extremely well done, which I have mentioned in recent interviews to other news outlets. However, I do not think the data in this paper resolve controversies about the validity of the amyloid cascade

Bruce Kagan on Amyloid beta protein forms ion channels: implications for Alzheimer's disease pathophysiology.

COMMENT This paper demostrates that Abeta forms ion channels in vivo, and that channel formation is integral to Abeta's cytotoxic properties. This is the critical extension of the in vitro work on Abeta ion channels to a cellular model. This paper shows that

Frank Bernier on Tackling Alzheimer’s from the Outside In

COMMENT While the data presented using antibodies is consistent with results obtained in other studies, I find the data using the gamma-secretase inhibitor DAPT doubtful. Oddo, et al., write "Using an alternative approach, we show that administration of the

Karen Hsiao Ashe on Tackling Alzheimer’s from the Outside In

COMMENT These are a series of beautifully done studies, which strongly support the Aβ cascade hypothesis. However, to fully understand the potential of Aβ reduction to alter the clinical course of Alzheimer’s disease, it would be important to know whether lowerin

Dave Morgan on Tackling Alzheimer’s from the Outside In

COMMENT There are two key features to this manuscript. The first is the obvious linkage between the presence of excess Aβ and the accumulation of early-stage phospho-tau variants. This is the first observation that reducing Aβ may slow the rate of tau filament fo

Gregory J. Brewer on Philadelphia: Can a Shrinking Brain Be Good for You?

COMMENT The summary by Gabrielle Strobel was nicely done. One further aspect from Sid Gilman's talk was that although a Z score for all cognitive tests showed the treatment group better than placebo as summarized, the ADAS-Cog score for the responder immuniz

Andre Delacourte on Alzheimer's Disease: A Re-examination of the Amyloid Hypothesis

COMMENT The amyloid cascade hypothesis (ACH) does not fit with the natural and molecular history of Alzheimer's disease. Major points: The first argument against the ACH is that tau and APP pathologies always grow in parallel in the human brain (Delacourte A

Mary Reid on What Flies Can Teach Us about Long-Term Memory—Cramming Helps

COMMENT Popovic, et al. (1), find that cathepsin L is capable of truncating cystatin C which they state has a much lower affinity for cysteine proteinases than the intact inhibitor. Might this occur in the Cer mutant and could that then result in increased cathep

Dieter Lütjohann on Philadelphia: All Is Not Well with the Statin Story

COMMENT 24S-hydroxycholesterol, an important oxidative cholesterol degradation product, can be used as a surrogate serum or CSF marker to monitor changes in brain cholesterol synthesis in humans and, with some restrictions, in animals. In serum samples, the conce