Thomas Bayer on Messing with the Membrane—An Alternative Interpretation of the Amyloid-β Hypothesis

COMMENT The very interesting review of Dr. Vincent Marchesi deals with the notion that Aβ, once generated by diverse secretases, never leaves the membrane and exerts its toxicity by yet unknown mechanisms. Supporting this view, we and others have seen evidence th

Dennis Selkoe on Messing with the Membrane—An Alternative Interpretation of the Amyloid-β Hypothesis

COMMENT within vesicular compartments of the cell or at the plasma membrane. Finally, I conclude with a comment

Raphael Kopan on A {gamma}-secretase-independent mechanism of signal transduction by the amyloid precursor protein.

COMMENT Amyloid precursor protein (APP), a γ-secretase substrate, was thought to have a nuclear function in regulating Tip60-mediated transcription. In this paper, the authors unequivocally demonstrate that APP proteolysis, and therefore nuclear translocation, ha

Gary Webb on Living and dying for sex. A theory of aging based on the modulation of cell cycle signaling by reproductive hormones.

COMMENT Exciting and novel. Will change the way we treat AD in the near future. 0 onthewebb

Brian Balin on The Pathogen Hypothesis—Challenging the Primacy of Genetics in Late-Onset Alzheimer Disease.

COMMENT Reply to Massimo Stefani by Brian Balin Dr. Stefani has responded to the background article with objections to arguments made in support of the pathogen hypothesis. While he admits that the microbial origin must be taken into consideration for some forms

Tommaso Russo on An alternative interpretation of the amyloid Abeta hypothesis with regard to the pathogenesis of Alzheimer's disease.

COMMENT It is quite surprising that, despite a huge number of experiments done and papers published, the molecular events responsible for the Alzheimer's phenotype remain obscure. This article is a stimulating exercise that gives support to an alternative ex

Tommaso Russo on Messing with the Membrane—An Alternative Interpretation of the Amyloid-β Hypothesis

COMMENT It is quite surprising that, despite a huge number of experiments done and papers published, the molecular events responsible for the Alzheimer's phenotype remain obscure. This article is a stimulating exercise that gives support to an alternative ex

Edward Koo on Messing with the Membrane—An Alternative Interpretation of the Amyloid-β Hypothesis

COMMENT As is often the case, an outsider can give fresh perspectives in ways that someone from the inside has difficulty seeing. In this article, Dr. Vincent Marchesi, a former member of the Alzheimer Research Forum Advisory Board, presented a very thoughtful pe

Edward Koo on An alternative interpretation of the amyloid Abeta hypothesis with regard to the pathogenesis of Alzheimer's disease.

COMMENT As is often the case, an outsider can give fresh perspectives in ways that someone from the inside has difficulty seeing. In this article, Dr. Vincent Marchesi, a former member of the Alzheimer Research Forum Advisory Board, presented a very thoughtful pe

Ruth Itzhaki on The Pathogen Hypothesis—Challenging the Primacy of Genetics in Late-Onset Alzheimer Disease.

COMMENT Brian Balin has written his Challenge so impressively, in particular stressing the insidious (though sporadic) nature of stealth microorganisms, that there is little to add except a few hopefully apposite points. Apropos of the extraordinary resistance of

Mary Reid on Of Cabbages and Rings—AD and the Vasculature

COMMENT Is it possible that coronary artery bypass grafting was more likely complicated by atrial fibrillation requiring digoxin therapy in those who later developed AD? I refer to my previous post in which I ask whether digoxin therapy may be a risk factor for t

John Trojanowski on Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment.

COMMENT This is an important study that confirms and extends prior chemical AD biomarker studies of CSF isoprostanes and tau while combining them with MRI to improve diagnosis of MCI. The work is significant because it bodes well for the success of the recently f

Andre Delacourte on Accelerated amyloid deposition, neurofibrillary degeneration and neuronal loss in double mutant APP/tau transgenic mice.

COMMENT These results fit well with the the tau/APP syngergy observed in the human brain (Delacourte et al., 2002). 0 andre.delacourte Nonoverlapping but synergetic tau and APP pathologies in sporadic Alzheimer's disease.

Samir Kumar-Singh on Amyloid-β—On or off the Wall?

COMMENT Regarding Dr. D’Andrea’s remarks, we studied only ThS-positive “dense” plaques and not diffuse plaques, as also suggested by the title “Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer disease are centered on vessel walls.” Within the text

George Martin on Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model.

COMMENT Readers should also consult a recent paper from the laboratory of Bart De Strooper and colleagues. Their data "challenge the general idea of BACE1 as a safe drug target..." 0 gmmartin