John Nambu on Behold the Power of Cheese

COMMENT The study by McKeown and colleagues describes a novel Drosophila gene— blue cheese —that is required for the survival of neurons in aging adult flies. They show that while homozygous blue cheese mutants survive into adulthood, they exhibit a 40-45 percent

Junying Yuan on Playing "Gotcha" with the Phantom: α-synuclein Oligos Spotted in Vivo

COMMENT This is a fascinating paper! It reveals a side of α-synuclein—an elusive neuron killer—which has escaped detection until now. This work may open a new chapter in the research of neurodegenerative diseases, namely, examining the role of lipids in preventin

Martha Clare Morris on One Thumb Up on Dietary Fat, One Down on Vitamins, Two Down on Estrogen

COMMENT I’d like to comment on the Luchsinger and the follow-up Rotterdam studies on fats, and the

Scott Small on A BOLD New Look at Neuronal MRI

COMMENT Although little more that a decade old, fMRI already has an established pantheon of "giants in the field." Seiji Ogawa, one of these giants, was the first to observe that when rodents breathe, 100 percent oxygen-diminished contrast is observed i

Roland Pochet on Neuroimaging and early diagnosis of Alzheimer disease: a look to the future.

COMMENT This paper should have a broad impact on clinicians and promote neuroimaging. 0 rpochet

Andre Delacourte on Repeat motifs of tau bind to the insides of microtubules in the absence of taxol.

COMMENT Controversial but exciting.... 0 andre.delacourte

Todd E. Golde on Epitope and isotype specificities of antibodies to beta -amyloid peptide for protection against Alzheimer's disease-like neuropathology.

COMMENT This is a study on a quite impressive scale that compares different isotypes of anti-Abeta antibodies with respect to efficacy in attenuating amyloid loads in PDAPP mice. The conclusion is anti-Abeta IgG with high affinity for Fc receptors are more effect

Takaomi Saido on Neuronal endosomal/lysosomal membrane destabilization activates caspases and induces abnormal accumulation of the lipid secondary messenger ceramide.

COMMENT Very provocative. It would be more relevant if the pathway is proven to be present in adult brain in an in vivo paradigm. 0 saido

Takaomi Saido on Generation of functional inhibitory neurons in the adult rat hippocampus.

COMMENT Interneurons will become more important in AD research for various reasons. One obvious reason is that the majority of dystrophic neurites in AD brains are likely to stem from interneurons. Brains lacking interneurons are like computers made only of diode

Takaomi Saido on Discovery of compounds that will prevent tau pathology.

COMMENT Tau is definately as important as Abeta as a preventive and therapeutic target for AD although paying too much attention to phoshphorylation is likely to be misleading for the following reason. The observations demonstrating that the PHF tau proteins in t

Takaomi Saido on Short-term administration of omega 3 fatty acids from fish oil results in increased transthyretin transcription in old rat hippocampus.

COMMENT Interesting work. Is the active ingredient DHA only? 0 saido

Junying Yuan on New Insights and Strategies for Treating PolyQ Disorders

COMMENT The accumulation of SCA7 in the knockin model could mean that the expanded polyQ forms oligomers that are invisible under the microscope. Depending on the endogenous level of SCA7, which apparently is very low, a critical threshold to form visible inclusi

Todd E. Golde on The Notch ligands, Delta1 and Jagged2, are substrates for presenilin-dependent "gamma-secretase" cleavage.

COMMENT The data presented here are similar to that presented at recent meetings by Taylor Kimberly, Dennis Selkoe and colleagues. Collectively these studies add to the growing list of gamma-substrates. The finding that Notch ligands may be substrates for gamma-s

Todd E. Golde on 22R-hydroxycholesterol and 9-cis-retinoic acid induce ATP-binding cassette transporter A1 expression and cholesterol efflux in brain cells and decrease amyloid beta secretion.

COMMENT Another paper suggesting with data that support the notion that changes in cellular cholesterol can influence Abeta production. Mechanistic insight is not provided. Nevertheless these data do further reinforce the complex regulation of APP processing and

Todd E. Golde on Apolipoprotein E epsilon4 allele, AD pathology, and the clinical expression of Alzheimer's disease.

COMMENT Clinical-Pathologic data that supports the hypothesis that APOE4 casues AD by influencing Abeta deposition. A nice example of how genetic, biochemical, pathologic, and animal modeling studies converge to support a unifying hypothesis. 0 tgolde