Ann M. Graybiel on Correlation between cognitive deficits and Abeta deposits in transgenic APP+PS1 mice.

COMMENT "This mouse model suggests a link between deposition of mAPP and mPS1 and cognitive impairment in transgenic mice, and suggests that one link may be deposition of Abeta in frontal cortex and hippocampus." 0 graybiel

Ann M. Graybiel on Distinguishable effects of presenilin-1 and APP717 mutations on amyloid plaque deposition.

COMMENT "This is a very interesting possible differentiation of APP and PS-1 involvement in accumulation of plaques in familial and APP717 mutation brains." 0 graybiel

Benjamin Wolozin on VLDL receptor polymorphism, cognitive impairment, and dementia.

COMMENT "Increasing data points to an important role for lipid metabolism in dementia. This paper brings together trinucleotide repeat polymorphisms and lipid metabolism in a very interesting manner. The outcome sheds light on the factors influencing vascula

Benjamin Wolozin on Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments.

COMMENT This provides important information linking phosphorylation of tau to production of paired helical filaments." 0 bwolozin

Alison Goate on The -48 C/T polymorphism in the presenilin 1 promoter is associated with an increased risk of developing Alzheimer's disease and an increased Abeta load in brain.

COMMENT "Interesting paper showing an association between risk for AD and a polymorphism in the promoter of PS1. The risk genotype is also associated with increased Ab load in the brain. These observations are consistent with the hypothesis that increased PS

Hiroshi Mori on Notch1 and amyloid precursor protein are competitive substrates for presenilin1-dependent gamma-secretase cleavage.

COMMENT "This may suggests an important clue to understand the physiological interaction, though indirect, between APP and Notch as the common substrate for PS. It must be co crucial if the PS content as an enzyme is constant. However, it still remains if th

Hiroshi Mori on Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles.

COMMENT "The mechanism for tauopathy must be elucidated and accumulated from multiple attacks. This article must be one of attractive targets though it is not established whether a fly cell is suitable for a model for human neurodegeneration in FTD brains.&q

Edward Koo on The amyloidogenic pathway of amyloid precursor protein (APP) is independent of its cleavage by caspases.

COMMENT The point of our paper was the surprising result from Gervais and colleagues that caspase cleavage of APP resulted in more, rather than less, A-beta. The five fold increase in A-beta was striking, making it comparable to the effects of the APP "Swedi

Benjamin Wolozin on The amyloidogenic pathway of amyloid precursor protein (APP) is independent of its cleavage by caspases.

COMMENT "This provides important information relevant to a continuing debate over the mechanisms underlying production of Ab." 0 bwolozin

Hiroshi Mori on The Alzheimer amyloid precursor protein (APP) and FE65, an APP-binding protein, regulate cell movement.

COMMENT "This is an interesting paper to show the physiological function of FE65 in cell movement and signal transduction. More related studies are expected to clarify an unknown activity of APP." 0 mori

John Hardy on SNP association studies in Alzheimer's disease highlight problems for complex disease analysis.

COMMENT "At last, a welcome attempt to try and deal with the problems of multiple testing in association studies." 0 J.Hardy

Benjamin Wolozin on Cholesterol-dependent formation of GM1 ganglioside-bound amyloid beta-protein, an endogenous seed for Alzheimer amyloid.

COMMENT "Any endogenous protein that degrades Abeta could be very important." 0 bwolozin

Benjamin Wolozin on Cholesterol accumulates in senile plaques of Alzheimer disease patients and in transgenic APP(SW) mice.

COMMENT "Increasing data implicates cholesterol in the pathophysiology of AD. This report examines the question from a neuropathological standpoint and shows a relationship between cholesterol and Ab deposition. However, it is possible that the significant l

Inez Vincent on Reduced protein phosphatase 2A activity induces hyperphosphorylation and altered compartmentalization of tau in transgenic mice.

COMMENT Kins et al, have done an important study on a rather neglected aspect of AD pathology, ie, the role of protein phosphatases. Their transgenic mouse model with reduced phosphatase 2A activity will be quite useful not only for further studies of tau phospho

Hiroshi Mori on The transmembrane domain of the Alzheimer's beta-secretase (BACE1) determines its late Golgi localization and access to beta -amyloid precursor protein (APP) substrate.

COMMENT "This presents a crucial result on the localization and function for BACE but the question remains open whether all of APP is not digested by BACE in distal Golgi membrane, ER, endosome or plasma membrane." 0 mori