Hiroshi Mori on Low prevalence of apolipoprotein E epsilon 4 allele in the neurofibrillary tangle predominant form of senile dementia.

COMMENT Tauopathy is an attractive study for the late AD pathogenesis and the effect of apoE e4 allele because the initial report published by Roses, A. and his colleagues described the enhancement of deposition of apoE by the binding of tau. 0 mori

Carl Cotman on Plaque biogenesis in brain aging and Alzheimer's disease. I. Progressive changes in phosphorylation states of paired helical filaments and neurofilaments.

COMMENT This is the first study to who that hyperphosphorlyated neurofilaments may precede tau hyperphosphorylation. 0 cwcotman

David Holtzman on Local and systemic increase in lipid peroxidation after moderate experimental traumatic brain injury.

COMMENT This paper is interesting as it suggests that there may be a biomarker for acute brain injury which is readily measurable from an easily obtainable source. 0 holtzman

Inez Vincent on Cyclin-dependent kinases and P53 pathways are activated independently and mediate Bax activation in neurons after DNA damage.

COMMENT This report is a continuation of a series of papers in which Dr Park and his colleagues attempt to unravel the intricacies of the cell cycle driven mechanism of neuronal apoptosis. The involvement of DNA damage in this process is especially important in l

Hiroshi Mori on New protease inhibitors prevent gamma-secretase-mediated production of Abeta40/42 without affecting Notch cleavage.

COMMENT It is an unexpected finding of the occurrence of an inhibitor to block APP-gamma secretase but not Notch processing. Although we do not know the physiological function of the soluble secreted amyloid protein, it is now potent to exclusively regulate APP m

Benjamin Wolozin on Presenilin-2 (PS2) expression up-regulation in a model of retinopathy of prematurity and pathoangiogenesis.

COMMENT This implicates PS2 in other mechanisms of neurodegeneration. 0 bwolozin

Edward Koo on Insulysin hydrolyzes amyloid beta peptides to products that are neither neurotoxic nor deposit on amyloid plaques.

COMMENT Further work on insulysin (insulin degrading enzyme) in proteolysis of amyloid peptide. 0 edkoo

Benjamin Wolozin on Sensitization of neuronal cells to oxidative stress with mutated human alpha-synuclein.

COMMENT Little is known about the biology of synuclein aggregation. 0 bwolozin

Richard Mayeux on Presenilin-1 regulates the neuronal threshold to excitotoxicity both physiologically and pathologically.

COMMENT This is an important study offering new insights to the mechanisms by with genetic mutations alter the function of proteins such as Presenilin. 0 rpm2

John Hardy on Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members.

COMMENT A heroic and painstaking study… but we still don't really know what APP does. 0 J.Hardy

Richard Mayeux on The preclinical phase of alzheimer disease: A 22-year prospective study of the Framingham Cohort.

COMMENT This suggests that a "preclinical phase" of Alzheimer's disease exists that precedes the diagnosis by 10 or more years. Others have found that individuals whose memory or other cognitive skills are comparatively weaker than their peers are

Richard Mayeux on Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1.

COMMENT Role of PS1/2 as interactive with gamma secretase. 0 rpm2

John Hardy on Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1.

COMMENT Now proven almost beyond reasonable doubt: presenilin = gamma secretase. The three papers almost establish beyond reasonable doubt that presenilins are the long-sort after gamma secretases. The questions that remain include what are the other components o

Hiroshi Mori on Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1.

COMMENT Further evidence is provided here to prove that PS1 is gamma-secretase. The next proof desired is a direct one. 0 mori

Benjamin Wolozin on Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1.

COMMENT Obiously important. 0 bwolozin