Hiroshi Mori on Melatonin alters the metabolism of the beta-amyloid precursor protein in the neuroendocrine cell line PC12.

COMMENT Melatonin is one of the endogenous factors to regulate neuronal differentiation and has interesting effects on neuronal metabolism. This is the first paper to show its effect on APP and A-beta turn-over in PC12. 0 mori

Paul Coleman on Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease.

COMMENT On the basis of the abstarct it appears that the prediction of synaptic change indicated by the title is based on comparisons among groups rather than correlations within groups 0 Paul_Coleman

Hiroshi Mori on Interaction of human alpha-Synuclein and Parkinson's disease variants with phospholipids. Structural analysis using site-directed mutagenesis.

COMMENT It is no doubt to see an interaction of alpha-Syn with the lipid fraction because alpha-Syn has been identified as a hydrophobic synaptic component. The urgent issue to know may be in the next step for alpha-Syn. 0 mori

Hiroshi Mori on Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype.

COMMENT Insulin levels are one indicator of sugar metabolism and could be associated with glycation or radical formation. In this particular sense, this paper may be interesting in clarification of amyloid formation mechanism. 0 mori

John Olney on Impairment of glucose and glutamate transport and induction of mitochondrial oxidative stress and dysfunction in synaptosomes by amyloid beta-peptide: role of the lipid peroxidation product 4-hydroxynonenal.

COMMENT I do not have an opinion regarding the importance of this line of research for elucidating the pathophysiology of AD. A major problem with much of the current research on amyloid beta-peptide is that the concentrations used experimentally to show that it

Benjamin Wolozin on Estrogen lowers Alzheimer beta-amyloid generation by stimulating trans-Golgi network vesicle biogenesis.

COMMENT This paper describes a novel mechanism for regulating Ab production. Many in the field often talk about the role of trafficking in APP processing, but this paper provides a nice example where Ab production is modulated via a trafficking mechanism, rather

Paul Coleman on New phosphorylation sites identified in hyperphosphorylated tau (paired helical filament-tau) from Alzheimer's disease brain using nanoelectrospray mass spectrometry.

COMMENT A potentially important work, especially when we know more about the significance of these phosphorylations for the functioning of the cell 0 Paul_Coleman

Elliott Mufson on Generation of Alzheimer beta-amyloid protein in the trans-Golgi network in the apparent absence of vesicle formation.

COMMENT Interesting. 0 emufson

Hiroshi Mori on Tau regulates the attachment/detachment but not the speed of motors in microtubule-dependent transport of single vesicles and organelles.

COMMENT A view is provided in living cells with and without exogenously transfected tau. It is interesting to see a mechanism for how kinesin attachs or detachs on microtubules with the aid of tau. 0 mori

Peter Davies on Sequential phosphorylation of Tau by glycogen synthase kinase-3beta and protein kinase A at Thr212 and Ser214 generates the Alzheimer-specific epitope of antibody AT100 and requires a paired-helical-filament-like conformation.

COMMENT We need the detailed phosphorylation mechanism of tau to understand cell death. This is but one tau study, but is a step towards knowing the molecular mechanism of dementia. 0 peter.davies

Edward Koo on Beta-secretase processing in the trans-Golgi network preferentially generates truncated amyloid species that accumulate in Alzheimer's disease brain.

COMMENT Interesting study. A bit surprising since glu11 cleaved Ab is not that abundant in vitro or in vivo. Or, maybe we just haven't looked at the glu11 enough? 0 edkoo

Benjamin Wolozin on Imaging brain amyloid of Alzheimer disease in vivo in transgenic mice with an Abeta peptide radiopharmaceutical.

COMMENT This is an example of an important evolving technology that could be useful for diagnosis. 0 bwolozin

Hiroshi Mori on Increased apolipoprotein E mRNA in the hippocampus in Alzheimer disease and in rats after entorhinal cortex lesioning.

COMMENT ApoE mRNA was found to be increased in astrocyte in lesioned brains but not in neurons. This suggests, at least, that some apoE could be astrocyte-origin. 0 mori

Hiroshi Mori on Genetic risk factors in Japanese Alzheimer's disease patients: alpha1-ACT, VLDLR, and ApoE.

COMMENT They examined many familial AD cases in Japan and confirmed published mutations. They are still looking for another gene(s) that bears the new mutation(s). 0 mori

Benjamin Wolozin on Alzheimer's disease. Bad for the heart, bad for the mind?

COMMENT This article discusses an emerging link between cholesterol and Abeta that could have therapeutic implications. 0 bwolozin