John Hardy on Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch.

COMMENT This, and the remarkable paper from from Francis and colleagues, mark real progress in the dissection of the gamma secretase complex... perhaps we are now close to knowing all it's components 0 J.Hardy aph-1 and pen-2 are required for Notch pathway s

Alexei Koudinov on Function of beta-amyloid in cholesterol transport: a lead to neurotoxicity.

COMMENT Unfortunately this study does not provide a fair discussion of the subject of 'cholesterol, amyloid beta and Alzheimer's disease'. There are many bibliography references to show that what authors' claim to be their novel idea is alread

Benjamin Wolozin on Function of beta-amyloid in cholesterol transport: a lead to neurotoxicity.

COMMENT There is an increasing connection between cholesterol and APP/Aβ. This is a provocative hypothesis. While it is likely that the toxicity of Aβ is pleitropic, the proposition that Aβ plays a role in cholesterol transport appears reasonable. 0 bwolozin

Larry Nault on Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease.

COMMENT I believe this study has the potential to accelerate active AD prevention. I'm puzzeled that the re-analysis of data (see 23 July 2002 news story) discerning between NSAIDs is taking so long to be published. This has to be seen as a CORRECTION, and a

David Holtzman on More Evidence for Dynamic PolyQ Aggregates

COMMENT Two new papers demonstrate several interesting findings that demonstrate that components of aggregated, polyglutamine-containing inclusions seen in certain neurodegenerative diseases are highly dynamic. Stenoien, et al., used fluorescence recovery after p

Alexei Koudinov on Polymorphism in the cholesterol 24S-hydroxylase gene is associated with Alzheimer's disease.

COMMENT Also please do not miss the following article that nicely extends the present study: Cholesterol and Alzheimer's disease. Neurobiology of Lipids Published 30 August 2002 [Full Text]. 0 postmaster Cholesterol and Alzheimer's Disease

Alexei Koudinov on What evidence would prove the amyloid hypothesis? Towards rational drug treatments for Alzheimer's disease.

COMMENT no amyloid is innocent. Some citations are provided below: Please see the following comments related

Alexei Koudinov on Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease.

COMMENT I recommend this article as well as the following related contribution: Alzheimer's disease and amyloid beta protein Koudinov AR et al. Science online, Published 25 June 2002; Amyloid hypothesis: summer 2002 and 8th International Conference on Alzhei

Alexei Koudinov on Explaining the cause of the amyloid burden in Alzheimer disease.

COMMENT I highly recommend this article BUT suggest readers to supplement unipolar viewpoint of Archives of Neurology Editor-in-Chief: Alzheimer's disease and amyloid beta protein Koudinov AR et al. Science online, Published 25 June 2002; Amyloid hypothesis:

Inez Vincent on Oxidative Stress Triggers Neuronal Cell-Cycle Reentry

COMMENT I loved this paper.This work makes a compelling case for the involvement of oxidative stress in unscheduled cell cycle re-entry of postmitotic neurons, with consequent apoptosis. What is remarkable is the selective vulnerability of cerebellar and retinal

Paul Coleman on Oxidative Stress Triggers Neuronal Cell-Cycle Reentry

COMMENT retina. The authors comment that "Similar to many gene products involved in neurodegenerative and

Leon Thal on Trials and Tribulations: Does ADAPT Have to Adapt?

COMMENT The addition of a third arm with ibuprofen is a consideration. It would be logistically difficult but possible to do. The real question is does ibuprofen make any more sense than naproxen since tolerated doses over five years may well be too low to block

Paul Aisen on Trials and Tribulations: Does ADAPT Have to Adapt?

COMMENT I have read the letter and was quite distressed by it. I am not involved in the ADAPT, though I have had a number of discussions with John Breitner about it, and have shared data from the ADCS NSAID study with the ADAPT investigators. Also, I was involved

Monique M.B. Breteler on Trials and Tribulations: Does ADAPT Have to Adapt?

COMMENT opinion on our research findings from the Rotterdam Study, which is why I would like to comment on their

Edward Koo on Trials and Tribulations: Does ADAPT Have to Adapt?

COMMENT Many of Sidney Wolfe's accusations of ADAPT are unfounded although I appreciate their caution that giving these drugs to elderly individuals can be potentially dangerous. I will focus only on those aspects that concern our work as I think our results