Vincent Marchesi on Messing with the Membrane—An Alternative Interpretation of the Amyloid-β Hypothesis
COMMENT Response by Vincent Marchesi to comments through 28 September 2005 Dr. Russo points out that if Aβ
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Vincent Marchesi on Nicastrin—A DAPper Role in γ-Secretase
COMMENT The strength of this paper is the imaginative use of carefully crafted recombinant peptides to study a complicated process that is difficult to approach using conventional cell biological techniques. But one also has to keep in mind that no "native&q
Vincent Marchesi on Amyloid Hypothesis—Closing the Spigot Helps, Temporarily
COMMENT This paper is one of the most interesting contributions of the year, and may well be one of the most informative animal models of AD yet published. To fully appreciate it, readers should first read two prior papers from this same group in which they syste
Vincent Marchesi on Alteration of protein kinase C conformation in red blood cells: a potential marker for Alzheimer's disease but not for Parkinson's disease.
COMMENT I can't say that I agree with Paul Coleman's evaluation of this work. The method of analysis is quite convoluted, and it is not at all clear what is causing the difference in fluorescence intensity at particular wave lengths. It is very unlikely
Vincent Marchesi on BACE overexpression alters the subcellular processing of APP and inhibits Abeta deposition in vivo.
COMMENT I agree with Martin and Gouras that this paper deserves serious study since it is an ambitious attempt to explore whether cleavage of APP at different subcellular sites determines whether Abeta peptides are ultimately toxic to the neurons in which the are
Vincent Marchesi on Longer forms of amyloid beta protein: implications for the mechanism of intramembrane cleavage by gamma-secretase.
COMMENT Using a modified gel electrophoresis system, these investigators describe a series of longer forms of amyloid-β peptides in both transfected cells and transgenic brain tissue. These peptides include some that are 45, 46, and 48 amino acids long, which the
Vincent Marchesi on FRETting Pays off—NSAIDs Target Presenilins, Reduce Aβ42
COMMENT I agree that this is a very impressive attempt to use the power of energy transfer techniques to study the effects of NSAIDs on the organization of the presenilin/γ-secretase complex. I am concerned that the fluorophores used to measure lifetimes could co
Vincent Marchesi on Forebrain degeneration and ventricle enlargement caused by double knockout of Alzheimer's presenilin-1 and presenilin-2.
COMMENT This work largely confirms the earlier conditional KO study by Saura et al., 2004. There is a dramatic reduction in cortical tissue and a massive hydrocephalic-like appearance in animals that lack both presenilins. I wonder how significant and relevant th
Vincent Marchesi on ABAD, aka ERAB: Mitochondrial Miscreant Returns
COMMENT This is an interesting but still incomplete story. This work dates back several years, when the authors found an unexpected ability of the Aβ peptide to bind to the enzyme alcohol dehydrogenase (ADH). It appears that the binding is relatively specific whe
Vincent Marchesi on A molecular switch in amyloid assembly: Met35 and amyloid beta-protein oligomerization.
COMMENT There are many reasons for believing that Aβ peptides, in one form or another, are important factors in the pathogenesis of AD. Although some investigators are skeptical that these peptide are necessarily the most important factors leading to this disease
Vincent Marchesi on Presenilin—Two Heads Better Than One?
COMMENT intramembranous peptides that allow them to escape into the cytosol. (VT Marchesi) vincent.marchesi 0
Vincent Marchesi on BACE Goes Rafting after APP
COMMENT I think this issue is worth exploring, but I am concerned that the ability of a GPI-BACE chimera to cleave APP may be too artificial a model to tell us much about how the authentic BACE behaves. GPI-linked peptides would be expected to partition in rafts
Vincent Marchesi on Coping with Copper—Minute Amount of Metal Plagues Rabbit Brain
COMMENT I have to agree completely with the comments of Exley. The illustrations purporting to demonstrate
Vincent Marchesi on Alzheimer's disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss.
COMMENT Small, soluble aggregates of the Aβ1-42 peptide are now believed to be the toxic factor that is responsible for synaptic dysfunction and eventual neuronal degeneration in Alzheimer's disease. This work adds to this consensus by showing that soluble e
Vincent Marchesi on Calbindin Study: Is Calcium the Molecular Handle on Dysfunction in AD?
COMMENT Amyloid peptide-induced behavioral deficits in transgenic models of Alzheimer's disease are tightly linked to depletion of calcium-dependent proteins in granule cells of the dentate gyrus. This work builds on earlier observations that described the r