Andre Delacourte on The APP intracellular domain forms nuclear multiprotein complexes and regulates the transcription of its own precursor.

COMMENT From this paper, one should ask—if AICD is dysregulated in AD—if yes, if this dysregulation is playing a role in the neurodegenerating process (loss of function of APP due to aberrrant nuclear signalling), and if amyloid is not a marker of this dysmetabol

Farhan Ul Haq Subhani on Staring into the Eyes of Death—Measuring Apoptosis One Neuron at a Time

COMMENT This is a good effort, and I think that it would be important in the field of retinal disease. It is clear that the retinal and hippocampal neurons are much different. Being sensitive to light, the retinal neurons have different physiological levels. Reti

Takaomi Saido on Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial.

COMMENT This work implies that MCI treatment, which is more preventive in nature than that AD treatment, requries a strategy that targets pathological events upstream of cholinergic neuorodegeneration. 0 saido

Takaomi Saido on A synthetic peptide blocking the apolipoprotein E/beta-amyloid binding mitigates beta-amyloid toxicity and fibril formation in vitro and reduces beta-amyloid plaques in transgenic mice.

COMMENT This work points to the possible central role of the ApoE-Abeta interaction in Abeta amyloidosis. Whether Abeta plaques, ApoE-Abeta complexes, or some other forms of Abeta oligomer is primarily neurotoxic remains an open question. 0 saido

Paul Reber on Memory Loss—Really Lost or Just Forgotten—New Test Decides

COMMENT A fundamental question about memory is: What happens to a memory after it is initially stored? Studies of patients with amnesia have found that a strengthening process known as consolidation must be occurring on some of our memories. While some memories f

shen chengyong on Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP.

COMMENT This paper provided us with a new function mechanism of APP, which may give us some clues as to how to decrease amyloid peptide while not disturbing the normal function. 0 shency791105

shen chengyong on A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltransferase Tip60.

COMMENT AICD is produced after the γ-secretase proteolysis process. It is similar to NICD as a transcript factor. This paper provides us with the information that APP may function by releasing AICD. Although the target gene of AICD is still unclear, it has been a

Kiminobu Sugaya on Increased Neurogenesis in AD? Evidence from APP Mice Strengthens Case

COMMENT This paper is a continuation of a study the authors published in the same journal. In their previous paper, they stated that transgenic mice expressing mutant forms of APP (22, 23) or presenilin-1 (41) show impaired, rather than increased, neurogenesis. T

Dora M. Kovacs on Caught in the Act: NPC1 Found to Bind Cholesterol

COMMENT This is an interesting paper in the cholesterol field. I can only agree with Tobias and Inez Vincent that the identification of the NPC1 sterol-sensing domain as a possible binding site for cholesterol may lead to new clues for protein-lipid interactions.

George Perry on Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology.

COMMENT Caspase Activation But Not Apoptosis The article by Rissman and colleagues (2004) and accompanying commentary by Dickson (2004) highlight the potential importance of caspase activation in Alzheimer disease (AD). In the former, Rissmann et al. (2004) convi

Inez Vincent on Caught in the Act: NPC1 Found to Bind Cholesterol

COMMENT Because of the accumulation of cholesterol in NPC patients having mutated NPC1, it has been assumed for many years that NPC1 is a cholesterol transporter. For the first time, the work of Ohgami et al. demonstrates a direct interaction between a cholestero

Kazuhiro Honda on Alzheimer's brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication.

COMMENT Mitochondria and Alzheimer’s Disease: A Complex Interrelationship Recently, Coskun and colleagues (2004) reported that brains from patients with Alzheimer's disease (AD) present somatic mtDNA control-region mutations, especially in individuals older

Takaomi Saido on Abeta is targeted to the vasculature in a mouse model of hereditary cerebral hemorrhage with amyloidosis.

COMMENT The work provides insights into the significance of conformational versus metabolic properties in the occurrence of pathological phenotypes, i.e., amyloid angiopathy versus parenchymal amyloidosis. 0 saido

Anatol Kontush on Alzheimer's brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication.

COMMENT Etiology of late-onset Alzheimer’s disease (AD) is unknown; the paper of Coskun et al. [1] lends further support to an exciting hypothesis that it may be caused by somatic mutations in mtDNA. Mitochondria have long been known as a major source of reactive

Gemma Casadesus on Neurogenic effect of beta-amyloid peptide in the development of neural stem cells.

COMMENT Neurogenesis in AD: Good, Bad or Ugly? Propelled by the Democratic National Convention, stem cell research and its potential as a therapeutic for neurodegenerative diseases such as Alzheimer disease (AD) is back in the headlines. However, often lacking fr