Tennore Ramesh on Tubulin Chaperone Found to Cause Rare Motor Neuron Degeneration, and More

COMMENT This paper mixes well with the dynamitin paper that was published some time back. Also, its chaperone function is definitely interesting. The only other chaperones studied in ALS are HSP70 and CCS. However, no mutations in any chaperones have been identif

Curtis Dobson on The Alzheimer's Vaccination Story, Continued

COMMENT We would like to add just two points—on aetiological and therapeutic rather than immunological aspects—to those of Robinson et al. Firstly, the paper by Hock et al. refers in the discussion to patients who developed "aseptic meningoencephalitis."

Manuel Menendez-Gonzalez on Rates of progression in mild cognitive impairment and early Alzheimer's disease.

COMMENT I agree. We need blood or CSF biomarkers to get early diagnosis. 0 manuelmenendez

Michael Wolfe on Nicastrin Mutations Selectively Modulate Notch Processing

COMMENT The results of this paper are very interesting and emphasize the critical role of nicastrin in PS-dependent γ-secretase activity. The problem is that the genetic findings are interpreted without adequate consideration of the biochemistry of γ-secretase. T

Tomiichiro Oda on A novel beta-sheet breaker, RS-0406, reverses amyloid beta-induced cytotoxicity and impairment of long-term potentiation in vitro.

COMMENT The compounds RS-0406 and others as yet undisclosed are available for licensing upon request. Contact yasuhiro@shina.sankyo.co.jp (Y. Nakagami) for more information. 0 odatom

Edward Koo on Presenilins mediate a dual intramembranous gamma-secretase cleavage of Notch-1.

COMMENT Nice study to show that Notch also undergoes similar "multiple" transmembrane cleavage like APP/abeta. The only concern is that the tag is artificial and it is unclear whether authentic Notch does the same thing. 0 edkoo

Edward Koo on Neurotoxic effects of thioflavin S-positive amyloid deposits in transgenic mice and Alzheimer's disease.

COMMENT Elegant study although I still wonder why it is so hard to kill neurons in rodent brain. It just seems curious to me that it takes that much effort to document neuronal loss. Also, when the amyloid deposits are that aggregated, is it "toxicity"

Edward Koo on Alzheimer's disease can be accurately diagnosed in very mildly impaired individuals.

COMMENT Nice confirmation of good clinical assessment. But, there's got to be a better (more efficient and reliable) way to diagnose early AD as potential new therapies enter the clinic. 0 edkoo

Edward Koo on Rates of progression in mild cognitive impairment and early Alzheimer's disease.

COMMENT The results are not surprising but reinforce the need for reliable biomarkers of disease progression and early diagnosis. 0 edkoo

Gunnar Gouras on Shape-Shifting Prion Protein in Cytosol: Highly Toxic Yet Almost Invisible

COMMENT The papers by Ma and Lindquist are important to AD research. Unlike most other neurodegenerative diseases, AD and prion diseases have in common that both are characterized by dementia and "extracellular" plaques. The present papers demonstrate t

David Holtzman on The Alzheimer's Vaccination Story, Continued

COMMENT Hock et al. show that in the human trial, in which subjects with AD were actively immunized with Aβ42, a percentage of these individuals develop anti-Aβ antibodies. The antibodies generated in this immunization protocol were predominantly against the N-te

Hui Zheng on Nicastrin Mutations Selectively Modulate Notch Processing

COMMENT Using genetic cross-breeding, Rozmahel et al. presented a novel finding that the presenilin 1 (PS1) developmental activity could be modified by genes located on the distal arm of chromosome 1. They further showed that one of the modifiers could be nicastr

Benjamin Wolozin on Presenilins mediate a dual intramembranous gamma-secretase cleavage of Notch-1.

COMMENT This is a very interesting paper that emphasizes the striking parallels between APP processing and Notch processing. 0 bwolozin

Benjamin Wolozin on Biochemical analysis of tau proteins in argyrophilic grain disease, Alzheimer's disease, and Pick's disease : a comparative study.

COMMENT This paper brings out a new tauopathy, which adds to the increasing list of tauopathies. 0 bwolozin

Benjamin Wolozin on Tau filament formation and associative memory deficit in aged mice expressing mutant (R406W) human tau.

COMMENT This work provides a valuable new model for familial tauopathies because it appears to provide important features lacking in other models. Specifically, these tau inclusions occur in the forebrain, unlike transgenic mice carrying P301L tau driven by the P