John Olney on Peroxynitrite modulates tyrosine phosphorylation and phosphoinositide signalling in human neuroblastoma SH-SY5Y cells: attenuated effects in human 1321N1 astrocytoma cells.

COMMENT Li et al describe the effects of peroxynitrite (free radical generated in nitric oxide pathways) on second messenger systems in cultured human tumor cells. Although the authors point to the possible relevance of their findings to AD, no direct link to AD

Elliott Mufson on Atrophy of the hippocampus, parietal cortex, and insula in Alzheimer's disease: a volumetric magnetic resonance imaging study.

COMMENT Interesting study. 0 emufson

Gerry Fischbach on Cholinergic activation of phosphoinositide signaling is impaired in Alzheimer's disease brain.

COMMENT Not clear what the PI signalling system does- the regional differences may be interesting. Which regions?- This is important. Are they the areas most affected by the disease? 0 gf224

Edward Koo on Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins.

COMMENT Another function for ps, also related to protein degradation but not like app or notch clevage. 0 edkoo

Paul Coleman on The order of exposure of tau to signal transduction kinases alters the generation of "AD-like" phosphoepitopes.

COMMENT The concept of sequential influence of kinases on successive phosphorylations of tau is an important one and this paper presents additional experimental clarification of the role of several kinases. 0 Paul_Coleman

Hiroshi Mori on In vitro peroxidase oxidation induces stable dimers of beta-amyloid (1-42) through dityrosine bridge formation.

COMMENT It is worth while to study oxidation function on amyloid toxicity and polymerization. 0 mori

Paul Coleman on Comparison of beta-protein/A4 deposits and Alz-50-stained cytoskeletal changes in the hypothalamus and adjoining areas of Alzheimer's disease patients: amorphic plaques and cytoskeletal changes occur independently.

COMMENT Although the data presented here are consistent with other studies, the interpretation of these data requires making assumptions about the life history of the A beta deposits and Alz 50 changes revealed by the methods used. 0 Paul_Coleman

Hiroshi Mori on Alzheimer disease: quantitative H-1 MR spectroscopic imaging of frontoparietal brain.

COMMENT Imaging analyses such as MRI can be powerful method for diagnosis and should become more useful when used with other biochemical analyses in the future. 0 mori

Elliott Mufson on Alzheimer's disease in twins.

COMMENT Noteworthy. 0 emufson

Benjamin Wolozin on Anti-amyloidogenic activity of tetracyclines: studies in vitro.

COMMENT Potential therapeutic approach in AD. Comes on the heals of Bush’s work showing that another antibiotic reduces plaque formation (through a chelation mechanism). 0 bwolozin

Carl Cotman on Brain blood flow in the dementias: SPECT with histopathologic correlation in 54 patients.

COMMENT Important 0 cwcotman

Hiroshi Mori on Modulation of nitric oxide production in human macrophages by apolipoprotein-E and amyloid-beta peptide.

COMMENT Little is known about accumulation after APOE spcies' cellular reactions. Such information is needed when we speculate APOE function on neuropathological cascade in Alzheimer's disease brain. 0 mori

Paul Coleman on A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain.

COMMENT The abstract states: 'Thus the targeting of gamma-secretase for the treatment of Alzheimer's disease may risk toxicity caused by reduced Notch signalling.' A potentially important cautionary note. 0 Paul_Coleman

Hiroshi Mori on Proteolytic release and nuclear translocation of Notch-1 are induced by presenilin-1 and impaired by pathogenic presenilin-1 mutations.

COMMENT This is clearl [evidence] for PS1's [role in the] function on cleavage and recruitment of Notch-1. Undoubtedly, this is one of the most important papers in this field. 0 mori

Paul Coleman on Cytoarchitectonic alterations in the supramarginal gyrus of late onset Alzheimer's disease.

COMMENT It is not clear whether the authors used appropriate unbiased stereological methods to estimate numbers of neurons, NFT and plaques. 0 Paul_Coleman