Kenneth Kosik on A novel method of generating neuronal cell lines from gene-knockout mice to study prion protein membrane orientation.

COMMENT The cell fusion looks really interesting, especially considering (1) the challenge of getting cellular models of AD, (2) the great number of constructs that need analysis, and (3) the otherwise difficult analysis of gene dosage. 0 kosik

Inez Vincent on Amyloid deposition in APP23 mice is associated with the expression of cyclins in astrocytes but not in neurons.

COMMENT I am submitting this invited comment with the caveat that I have not had an opportunity to read

Roderick Jensen on A mechanism of cyclin D1 action encoded in the patterns of gene expression in human cancer.

COMMENT This paper is a nice illustration of how large, diverse data sets of high-quality microarray data can be mined for evidence to support novel hypotheses of gene function and regulation. We have recently been performing similar studies of common gene expres

Vincent Marchesi on Alzheimer's disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss.

COMMENT Small, soluble aggregates of the Aβ1-42 peptide are now believed to be the toxic factor that is responsible for synaptic dysfunction and eventual neuronal degeneration in Alzheimer's disease. This work adds to this consensus by showing that soluble e

Ruth Itzhaki on Are Neurons Just Too Laissez-Faire about Repair?

COMMENT   I was sorry not to be able to participate in the forum on DNA repair on Monday, but I wonder if anybody was aware that we worked on that topic some years ago (published between about 1987 and 1993). It was on gamma-irradiation of lymphocytes, looking at

liu qiang on Increased extracellular amyloid deposition and neurodegeneration in human amyloid precursor protein transgenic mice deficient in receptor-associated protein.

COMMENT Very good paper! 0 liuqiang

Robert Peers on Changing Channels—Modifier Gene Renders Mutation Lethal

COMMENT What really stumps scientists is scientific method, which means that to find the cause of Sporadic Alzheimer's, you need to go back to Isaac Newton or Charles Darwin, who used exclusively inductive reasoning. Late-onset AD is simply not genetic, exce

Thomas Beach on Cholinergic Systems and AD: Dark Clouds and Silver Linings

COMMENT This is an important finding that adds to the human evidence pointing to a cholinergic-amyloid connection. Our group has contributed by showing that both muscarinic agonists and acetylcholinesterase inhibitors lower CSF and cortical ABeta levels in normal

Mariano Alvira on Linking APP with Cell Cycle Reentry and Apoptosis—One Kinase Does the Trick

COMMENT We have made an antibody to an orphan GPCR that stains very strongly human neurons with NFT and human platelets. Anybody interested in collaborating? Mariano Alvira, MD marianoa@lsbio.com 206-374-1180 gvdnft 0

Pam mikeworth on Repairing Damaged Tissues—Viruses Get into the Akt

COMMENT While I am not a scientist, I can understand from your article that in the laboratory you are making progress with production of new healthy tissue in situations which have in the past not been possible to the extent you have seen here. I am 53 years old

Fred van Leeuwen on The temporal localization of frame-shift ubiquitin-B and amyloid precursor protein, and complement proteins in the brain of non-demented control patients with increasing Alzheimer's disease pathology.

COMMENT Currently there are around 20 different putative contributors related to the neuropathogenesis of Alzheimer’s disease (see ARF Current Hypotheses). In the paper by Konishi, et al., two of them are linked, i.e., frameshift and complement proteins. Several

Inez Vincent on Linking APP with Cell Cycle Reentry and Apoptosis—One Kinase Does the Trick

COMMENT McPhie et al. have done a beautiful job unraveling the signaling pathway linking FAD mutants of APP and neuronal apoptosis. Their evidence that reentry into the cell cycle is an obligatory step in this APP-induced apoptotic cascade is compelling. I'm

John Trojanowski on Toward a molecular neuropsychiatry of neurodegenerative diseases.

COMMENT Many neurodegenerative diseases share an enigmatic symmetry, i.e. missense mutations in the gene encoding the disease protein cause a familial variant of the disorder as well as its hallmark brain lesions, but the same brain lesions also form from the cor

Gemma Casadesus on Blueberries for All?

COMMENT Dietary Antioxidants and Alzheimer Disease Gemma Casadesus, Mark A. Smith and George Perry While little is known about the mechanisms responsible for the neuronal degeneration seen during Alzheimer’s disease (AD), the progressive, age-related inability of

Christopher Larsen on Proteasome Implicated in Axon Degeneration

COMMENT This interesting manuscript attempts to delineate a relationship between the ubiquitin system and the axonal degeneration of cultured neurons. Strongly presented data suggests that inhibition of proteases results in the marked slowing of this degeneration