Mary Reid on Telomerase mediates the cell survival-promoting actions of brain-derived neurotrophic factor and secreted amyloid precursor protein in developing hippocampal neurons.

COMMENT It's very interesting that Fu and colleagues report that their findings "demonstrate a requirement for telomerase in the cell survival-promoting actions of BDNF and sAPP in early postmitotic hippocampal neurons." Kharbanda et al. (1) report

Paul Coleman on Glycogen synthase kinase-3 is increased in white cells early in Alzheimer's disease.

COMMENT This paper adds an important molecule to the list of molecules found to be affected in peripheral cells in AD, and is consistent with a suggestion that AD is a systemic disease. 0 Paul_Coleman

Paul Coleman on Memory complaints in nondemented men predict future pathologic diagnosis of Alzheimer disease.

COMMENT A number of other studies have indicated that various measures of cognition may predict future clinical diagnosis of AD. Such data may be interpreted in a variety of ways. The present paper is important for limiting the number of tenable hypotheses that m

Paul Coleman on Expression profiling in laser-microdissected hippocampal subregions in rat brain reveals large subregion-specific differences in expression.

COMMENT This paper emphasizes differential expression of a large number of transcripts in CA3 and dentate gyrus. It appears that the samples that were laser microdissected contained cellular elements in addition to neurons. The authors used in situ hybridization

Paul Coleman on Identifying subtle interrelated changes in functional gene categories using continuous measures of gene expression.

COMMENT Methods of analysis of array data is a continually developing field. These authors present an analytical method they claim to be more effective than others in revealing subtle relationships of gene expression. 0 Paul_Coleman

Vincent Marchesi on FRETting Pays off—NSAIDs Target Presenilins, Reduce Aβ42

COMMENT I agree that this is a very impressive attempt to use the power of energy transfer techniques to study the effects of NSAIDs on the organization of the presenilin/γ-secretase complex. I am concerned that the fluorophores used to measure lifetimes could co

Takaomi Saido on Endothelin-converting enzyme-1 is expressed in human cerebral cortex and protects against Alzheimer's disease.

COMMENT This work provides a pathological support to the finding by Eckman et al., who showed that ECE is involved in Aβ degradation in vivo. 0 saido

Takaomi Saido on The presenilin C-terminus is required for ER-retention, nicastrin-binding and gamma-secretase activity.

COMMENT This work has taken the research community one step closer to understanding the integrity of the structure-function relationship of γ-secretase. 0 saido

Jürgen Götz on Controlling Tau—Phosphatases and Proteases PACK a Punch

COMMENT Of the diverse range of posttranslational modifications of tau (reviewed by us in Chen et al., 2004), serine/threonine-directed phosphorylation and truncations are among the most intensely studied, yet the role of their relative contribution to the tau pa

Paul Coleman on Microscopy Shifts to the Fast Lane with "Cytological Profiling"

COMMENT This paper represents a significant advance that was achieved by putting together a number of existing concepts to produce what may be considered an approach to a cell biological equivalent of nucleotide or cDNA arrays. The basic design involved culturing

Jie Shen on CPG2: a brain- and synapse-specific protein that regulates the endocytosis of glutamate receptors.

COMMENT This is a very nice paper! Using a thorough, systematic approach, the authors found that cpg2, a gene they previously identified to be upregulated by kainic acid-induced seizures, encodes a protein localized specifically to an endocytic zone within spines

Ruth Itzhaki on San Diego: HIV and AD—Save the Body, Lose the Mind?

COMMENT It was good to read the report on the AIDS study presented at San Diego by Lynn Pulliam and colleagues, because her poster on this topic at the International AD conference in Philadelphia in July might not have been seen by many. However, it is worth ment

Henry Paulson on A Step Toward Therapeutic RNA Interference

COMMENT Immediately following the description that RNA interference (RNAi) works in mammalian cells, it was recognized that such specific inhibitors of gene expression held tremendous potential as drugs (1). A wealth of papers describing the inhibition of disease

Mark Cookson on A Step Toward Therapeutic RNA Interference

COMMENT Many groups have adopted siRNA or shRNA technologies as the method of choice for gene knockdown since it was first demonstrated that these techniques work for mammalian cells. Although there are previous demonstrations that one can inject siRNA duplexes a

Luc Buee on Accepting its random coil nature allows a partial NMR assignment of the neuronal Tau protein.

COMMENT The NMR approach of studying tau protein is opening new perspectives in tau biology and therapeutic strategies of tau aggregation. 0 Luc.Buee