Andre Delacourte on Identification of amino-terminally cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration.

COMMENT Great and useful findings, if validated by others. 0 andre.delacourte

Beka Solomon on Antiinflammatory Drugs Protect Hippocampal Neurogenesis

COMMENT These two recent exciting studies demonstrate that local inflammation inhibits adult neurogenesis in the hippocampus in different diseased animal models [1,2]. The suppression of hippocampal neurogenesis by activated microglia may explain the cognitive dy

Remi Quirion on Target BACE: Better Than Ever?

COMMENT This new report by Ohno et al. demonstrates further that BACE1, an enzyme involved in the maturation of the APP precursor and the generation of amyloid peptides, is a potential therapeutic target toward the treatment of Alzheimer's disease. In mice i

Rebecca J. Henderson on Copper to the Rescue?

COMMENT Comment by Rebecca J. Henderson and James R. Connor Much attention has been paid to the link

Rebecca J. Henderson on Coping with Copper—Minute Amount of Metal Plagues Rabbit Brain

COMMENT Comment by Rebecca J. Henderson and James R. Connor Much attention has been paid to the link

Gerardo Morfini on Decreased cyclin-dependent kinase 5 (cdk5) activity is accompanied by redistribution of cdk5 and cytoskeletal proteins and increased cytoskeletal protein phosphorylation in p35 null mice.

COMMENT I have just read this JN paper on cdk5 regulation and I found it to be one of the best papers on this issue out there. I truly want to express my satisfaction for describing phenomena many others have overseen just for the fact of being in agreement with

Philip Wong on Target BACE: Better Than Ever?

COMMENT Previous studies showed that the deletion of BACE1 abolished the production of Aβ and BACE1 knockout mice are apparently normal. In this current paper, Ohno et al tested whether cognitive deficits occurring in the mutant APP mice (Tg2576) can be ameliorat

Raphael Kopan on Signal peptide peptidase forms a homodimer that is labeled by an active site-directed gamma-secretase inhibitor.

COMMENT The hypothesis we presented last year suggested that γ-secretase is a dimeric enzyme. This receives further support with strong biochemical data demonstrating that, like presenilin 1, signal peptide peptidase (SPP, a closely related aspartyl iCLiP) exists

Jie Shen on Target BACE: Better Than Ever?

COMMENT This is an interesting paper, and these mice are very useful for addressing a number of issues. The behavioral paradigms the authors chose to use are not the strongest learning and memory tests available; more robust and better established hippocampal-dep

Andre Delacourte on Value of CSF beta-amyloid1-42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment.

COMMENT A very useful biological confirmation that the drop of Abeta 1-42 in the CSF of MCI patients predicts the coming of Alzheimer's disease. 0 andre.delacourte

Andre Delacourte on Living with the enemy: a physiological role for the beta-amyloid peptide.

COMMENT Abeta is the principal marker for the pathogenesis of Alzheimer's disease. For the etiological responsability, as for justice, suspicion does not make culpability. Numerous other hypotheses describing how Abeta could kill the neuron have already been

Hui Zheng on Target BACE: Better Than Ever?

COMMENT Ohno et al. bred the BACE1 knockout (BACE1-/-) mice onto the Tg2576 APP transgenic background and tested the effects of BACE1 deficiency on Aβ production, behavioral performance, and cholinergic function at a young age (4-6 months), prior to amyloid plaqu

Michael Irizarry on Target BACE: Better Than Ever?

COMMENT This elegant report further supports BACE1 as a rational therapeutic target for treating the cerebral amyloidosis of Alzheimer's disease (AD). Ohno and colleagues eliminated BACE1 function in a mouse model of AD by crossing Tg2576 mice—which overexpr

Karen Chen on Target BACE: Better Than Ever?

COMMENT By Dione Kobayashi and Karen Chen The paper by Disterhoft et al. reporting cognitive and cholinergic rescue with their BACE1 knockout mice on a mutant hAPP background is extremely exciting and is a strong validation of BACE inhibitory strategies for Alzhe

Fred Van Leuven on Target BACE: Better Than Ever?

COMMENT This is exactly what we predicted (Dewachter and Van Leuven, 2002) or, as the Americans would put it, "what the doctor ordered…" The overall message of this study is loud and clear: BACE is hereby proven to be the favorite target for drug-makers