Benjamin Wolozin on The apoE receptor apoER2 is involved in the maintenance of efficient synaptic plasticity.

COMMENT This is interesting because recent manuscripts indicate that some of the ApoE receptors (e.g., R11) are increased in AD. 0 bwolozin

Takaomi Saido on Peroxisome-proliferator-activated receptor gamma induces a clearance mechanism for the amyloid-beta peptide.

COMMENT This work may open a new avenue for prevention and treatment through regulating Aβ levels in the brain. It would be interesting to know the mechanism by which PPARγ activation leads to the decrease of Aβ levels. 0 saido

Andre Delacourte on Hyperphosphorylation-induced self assembly of murine tau: a comparison with human tau.

COMMENT Interesting paper dealing with an important but not often discussed physiopathological point: Alzheimer disease is specific to humans. Why? 0 andre.delacourte

Ruth Itzhaki on Statins lower the risk of developing Alzheimer's disease by limiting lipid raft endocytosis and decreasing the neuronal spread of Herpes simplex virus type 1.

COMMENT commented on the support for a role of infectious agents in AD afforded by the intriguing similarities among

Benjamin Wolozin on Obesity-related leptin regulates Alzheimer's Abeta.

COMMENT This manuscript demonstrates a fascinating link between lipid homeostasis and APP processing. Previous work shows that BACE activity is modulated by cholesterol, and loss of presenilins change the metabolism of long chain fatty acids. This manuscript adds

Mary Reid on Cytosolic phospholipase A2 mediates neuronal apoptosis induced by soluble oligomers of the amyloid-beta peptide.

COMMENT Kriem and colleagues report that soluble oligomeric forms of amyloid peptide induce cytoplasmic PLA2 with subsequent neuronal apoptosis, which is reduced by inhibitors of p38. It's of interest that c-Abl is an activator of p38 MAP kinase (1). Might w

Nathaniel Milton on Enhanced toxicity and cellular binding of a modified amyloid beta peptide with a methionine to valine substitution.

COMMENT This paper has some interesting results and some elegant experimentation. However, I would like to propose an alternative interpretation of the results obtained for inhibition of amyloid-β toxicity by catalase. Zhang et al. have demonstrated that catalase

Nikolaos Tezapsidis on Obesity-related leptin regulates Alzheimer's Abeta.

COMMENT Can we prevent AD by treating obesity? In a recent study, it was determined that women who have been obese throughout their lives are more likely to lose brain tissue in the temporal lobe compared with women of normal weight (12). In this paper, we highli

Takaomi Saido on Longitudinal observation on CSF Abeta42 levels in young to middle-aged amyloid precursor protein/presenilin-1 doubly transgenic mice.

COMMENT This work may contribute to the establishment of a presymptomatic diagnosis of Alzheimer disease. 0 saido

Takaomi Saido on Insulin resistance contributes to aberrant stress responses in the Tg2576 mouse model of Alzheimer's disease.

COMMENT This work showing the possible relationship between insulin resistance and stress responses in AD model mice may provide a basis to explain why diabetes can be a risk factor for AD development, if the epidemiological notion is indeed universally true. 0 s

Takaomi Saido on Hemoglobin promotes Abeta oligomer formation and localizes in neurons and amyloid deposits.

COMMENT This is an interesting observation, but if the mechanism involves "circulation leakage," other plasma amyloidogenic proteins such as amyloid P component, insulin, and immunoglobulin would also contribute to Aβ amyloidosis. If Hb is a specific/se

Valentina Echeverria on Sharpen Your Synapses with Rolipram!

COMMENT Arancio, first author Bing Gong, and colleagues show evidence that Rolipram improved synaptic and cognitive functions in an Alzheimer mouse model. The cAMP/PKA/CREB pathway controls CREB-dependent gene expression, which is fundamental for neuronal surviva

Mark Cookson on Lentiviral vector delivery of parkin prevents dopaminergic degeneration in an alpha-synuclein rat model of Parkinson's disease.

COMMENT This elegant paper extends observations previously made in tissue culture (Petrucelli et al., 2002; Oluwatosin-Chigbu et al., 2003; Chung et al., 2004) and Drosophila (Yang et al., 2003; Haywood and Stavely, 2004) models of α-synuclein toxicity, namely th

Stephen D. Ginsberg on Microscopy Shifts to the Fast Lane with "Cytological Profiling"

COMMENT In a recent technological advance published in the journal Science by Z.E. Perlman et al., the group provides convincing evidence of the use of high-throughput cytological profiling by automated microscopy. This system is essentially a combination of micr

Gary Bassell on On-Demand Dendritic Proteins Served Up with Help of Fragile X Protein

COMMENT Various forms of mental retardation and neurodegenerative disorders are associated with defects in the density and morphology of dendritic spines (Fiala et al., 2002). Fragile X syndrome (FXS), the most common inherited cause of mental retardation, is cha