Hiroshi Mori on Apolipoprotein E promotes the binding and uptake of beta-amyloid into Chinese hamster ovary cells in an isoform-specific manner.

COMMENT We may wish to see an active action by allele 4 but not by the passive action by alleles 3 and 2 though. 0 mori

Carl Cotman on Participation of presenilin 2 in apoptosis: enhanced basal activity conferred by an Alzheimer mutation.

COMMENT An important study. See also Deng, et al in FEBS Letters 397 (1996) 50-54 0 cwcotman

Edward Koo on Endoplasmic reticulum stress-induced cysteine protease activation in cortical neurons: effect of an Alzheimer's disease-linked presenilin-1 knock-in mutation.

COMMENT More evidence against the stress response role of ps. Curious that the ps knock in mice show very little deficits. 0 edkoo

Hiroshi Mori on Heparan sulfate proteoglycan is associated with amyloid plaques and neuroanatomically targeted PrP pathology throughout the incubation period of scrapie-infected mice.

COMMENT Heparan sulfate proteoglycan (HSPG) may play a common role in the pathogenesis of AD and prion disease. 0 mori

Hiroshi Mori on Post-ischemic changes in the expression of Alzheimer's APP isoforms in rat cerebral cortex.

COMMENT The molecular change in APP isoform and expression should reflect neuronal and glial proliferation. The paper is interesting because the ischemic animal is a good model for showing such neuronal changes. 0 mori

Nikolaos K. Robakis on The HHQK domain of beta-amyloid provides a structural basis for the immunopathology of Alzheimer's disease.

COMMENT This paper offers an interesting idea for future strategies of AD therapy which could exploit the HHQK sequence to block plaque-induced microgliosis in AD. 0 nikos.robakis

Paul Coleman on Regulation of expression, phosphorylation and biological activity of tau during differentiation in SY5Y cells.

COMMENT The abstract of this paper suggests that phosphorylation of tau at the 12E8 epitope (Ser 262/356) epitope does not play a significant role in microtubule binding in differentiated SY5Y cells. This finding needs to be viewed in light of earlier work indica

Paul Coleman on Presenilins and Alzheimer's disease: the role of A beta 42.

COMMENT The discussion in this paper centers around csf markers. However, as the authors point out, a spinal tap is not appropriate as a routine part of the physical exam for diagnosis of AD in the preclinical phase- before large numbers of neurons are lost and w

Paul Coleman on Hyperphosphorylated tau in SY5Y cells: similarities and dissimilarities to abnormally hyperphosphorylated tau from Alzheimer disease brain.

COMMENT This paper suggests that 'hyperphosphorylated tau from SY5Y cells-is not lethal to the SY5Y cells because of its ion tau/HMW MAP ratio.' Other potential explanations of this non-lethality are also possible. 0 Paul_Coleman

Hiroshi Mori on Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity.

COMMENT Unquestionably this is a core paper for AD study. 0 mori

Elliott Mufson on Heparin promotes beta-secretase cleavage of the Alzheimer's amyloid precursor protein.

COMMENT Interesting. 0 emufson

Hiroshi Mori on Presenilin 1 facilitates the constitutive turnover of beta-catenin: differential activity of Alzheimer's disease-linked PS1 mutants in the beta-catenin-signaling pathway.

COMMENT It is necessary for us to know the molecular link between PS-1 and gene products involved in development from the viewpoint of possible therapy. GSK-3 and b-catenin are among the most plausible species to regulate PS-1 function. 0 mori

Richard Mayeux on Nasal administration of amyloid-beta peptide decreases cerebral amyloid burden in a mouse model of Alzheimer's disease.

COMMENT These add strong support to the notion that therapy targeting amyloid-beta may be an effective treatment for Alzheimer's disease. 0 rpm2

Hiroshi Mori on Presenilin 1 associates with glycogen synthase kinase-3beta and its substrate tau.

COMMENT GSK-3 is proposed to be located at the upstream of pathology from the binding of presenilin-1. The total cascade will go to more complex but interesting issue. 0 mori

Hiroshi Mori on Neuronal DNA damage precedes tangle formation and is associated with up-regulation of nitrotyrosine in Alzheimer's disease brain.

COMMENT TUNEL staining is beginning to be popular in AD research. This is the first document to explain the relationship between DNA damage and tangle formation. 0 mori