Edward Koo on FAD mutations in presenilin-1 or amyloid precursor protein decrease the efficacy of a gamma-secretase inhibitor: evidence for direct involvement of PS1 in the gamma-secretase cleavage complex.

COMMENT Interesting followup study. Still more smoke but where is the gun? 0 edkoo

John Olney on Stable complexes involving acetylcholinesterase and amyloid-beta peptide change the biochemical properties of the enzyme and increase the neurotoxicity of Alzheimer's fibrils.

COMMENT Alvarez et al report that acetylcholinesterase (ACHE) forms stable complexes with amyuloid-beta and that this transforms the chemical properties of ACHE and increases the neurotoxicity of amyloid beta aggregates. This is interesting but it is difficult to

Hiroshi Mori on Down's syndrome is associated with increased 8,12-iso-iPF2alpha-VI levels: evidence for enhanced lipid peroxidation in vivo.

COMMENT This is further evidence to show the involvement of in vivo lipid peroxidation in the course of Down's syndrome pathology. 0 mori

Hiroshi Mori on Discontinuous distribution of senile plaques within striate cortex hypercolumns in Alzheimer's disease.

COMMENT The visual system is one of the most well-known neuronal networks. Studies if the relationship between visual cortex and AD pathology may provide insight on the physiological significance of pathological changes in the disease. 0 mori

Edward Koo on Reduced effectiveness of Abeta1-42 immunization in APP transgenic mice with significant amyloid deposition.

COMMENT This makes more sense. I never understood how dense plaques can just melt away after immunization. 0 edkoo

Edward Koo on Receptor-dependent cell stress and amyloid accumulation in systemic amyloidosis.

COMMENT RAGE APPEARS TO BE THE RECEPTOR FOR VARIOUS AMYLOIDOSIS. THIS LAB CONTINUES SHOW TANTALIZING CLUES ABOUT RAGE IN CELL DYSFUNCTION. HOWEVER, HAS THERE BEEN INDEPENDENT CONFIRMATION OF THIS INTERACTION AND ITS RELEVANCE TO AD OR OTHER NEURODEGENERATIVE COND

Hiroshi Mori on Stable association of presenilin derivatives and absence of presenilin interactions with APP.

COMMENT The authors claim the lack of the interaction between APP and presenilin which has been expected widely. Since the the positive results were also reported by other groups, this must be an issue to study more by several viewpoints. 0 mori

Hiroshi Mori on Suppression of A beta-induced monocyte neurotoxicity by antiinflammatory compounds.

COMMENT Anti-inflammatory therapy may be a clue as a treatment of AD. The concrete evidence to support this is attractive and welcome. 0 mori

Paul Coleman on The magnitude of brain lipid peroxidation correlates with the extent of degeneration but not with density of neuritic plaques or neurofibrillary tangles or with APOE genotype in Alzheimer's disease patients.

COMMENT 'These data suggest that the magnitude of brain lipid peroxidation is closely related to the extent of brain degeneration in AD but is not significantly influenced by the density of neuritic plaques or neurofibrillary tangles--'. This appears to

Hiroshi Mori on No man alone: the rediscovery of Alois Alzheimer's original cases.

COMMENT It is highly interesting due to the original report to start AD clinical study and pathology. 0 mori

Benjamin Wolozin on alpha-Synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells.

COMMENT Although understanding factors regulating aggregation of a-synuclein is perhaps the most relevant issue to neurodegeneration, understanding the normal function and regulation of a-synuclein remains fundamentally important to the field. Insights into synuc

Paul Coleman on cAMP-dependent protein kinase phosphorylations on tau in Alzheimer's disease.

COMMENT The authors generated "highly specific monoclonal antibodies, CP-3 and PG-5, which recognize the PKA-dependent phosphorylations of ser214 and ser409 in tau respectively.--- neither site appears to be phosphorylated to any appreciable extent in normal

Elliott Mufson on Educational level and neuropsychological heterogeneity in dementia of the Alzheimer type.

COMMENT Interesting 0 emufson

Hiroshi Mori on Predicting the in vitro toxicity of synthetic beta-amyloid (1-40).

COMMENT Congo red is a good tool to monitor amyloid fibril formation. Beside the relationship between fibril formation and toxicity of amyloid peptide, it is useful to distinguish two states (fibrils or non-fibrils) of amyloid protein. 0 mori

Inez Vincent on Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment.

COMMENT Does this imply that atrophy and loss of layer II entorhinal cortex neurons are not part of the disease process, and are not to be taken as early indicators of AD pathology? 0 ivincent