Benjamin Wolozin on Cholesterol-dependent modulation of tau phosphorylation in cultured neurons.

COMMENT "Increasing data suggests that cholesterol plays an important role in AD. Most studies suggest that lowering cholesterol will protect against AD by reducing Abeta production. However, some studies show that people with low cholesterol are also at ris

John Hardy on Growth arrest of individual senile plaques in a model of Alzheimer's disease observed by in vivo multiphoton microscopy.

COMMENT An amazing technology used to show, once and for all, that plaques are dynamic structures. A great paper which subverts the huge literature seeking to correlate plaque numbers with clinical features. Pathology does not wait around to be counted!!!" 0

Edward Koo on Coexpression of human cdk5 and its activator p35 with human protein tau in neurons in brain of triple transgenic mice.

COMMENT "Surprising in vivo evidence that cdk5 may not phosphorylate tau in brain." 0 edkoo

Edward Koo on Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice.

COMMENT "Good in vivo experimental evidence of GSK phosphorylating tau. Previously, most brain evidence has been correlative." 0 edkoo

Benjamin Wolozin on Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice.

COMMENT "This paper provides in vivo support for a putative role of GSK in the regulation of catenin and tau phosphorylation." 0 bwolozin

Benjamin Wolozin on Age-dependent changes in brain, CSF, and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer's disease.

COMMENT "This clarifies the pathophysiology of Ab greatly." 0 bwolozin

John Hardy on Mice deficient in BACE1, the Alzheimer's beta-secretase, have normal phenotype and abolished beta-amyloid generation.

COMMENT "An excellent paper, not only establishing BACE as b-secretase but also suggesting that knockout (or, by implication drug inhibition) may not have major adverse effects." 0 J.Hardy

Benjamin Wolozin on The beta-amyloid precursor protein functions as a cytosolic anchoring site that prevents Fe65 nuclear translocation.

COMMENT "FE65 is a protein that is associated with APP. The role of this association is poorly understood – as is the role of APP. The observation that APP regulates FE65 function is therefore quite important." 0 bwolozin

Edward Koo on Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein.

COMMENT Very nice study even though the result is somewhat predictable. However, given the previous study showing aggregates after over-expression of just wild type synuclein, this study is an important contribution. 0 edkoo

Edward Koo on A non-amyloidogenic function of BACE-2 in the secretory pathway.

COMMENT Largely confirmatory results but noteworthy nonetheless. 0 edkoo

John Hardy on Inclusion body myositis-like phenotype induced by transgenic overexpression of beta APP in skeletal muscle.

COMMENT A fascinating paper which starts to move the study of inclusion body myositis on from phenomenology. 0 J.Hardy

John Hardy on Tau is essential to beta -amyloid-induced neurotoxicity.

COMMENT An interesting paper... it would be good to know, though, whether tau was "essential" to other forms of induced neurotoxicity. 0 J.Hardy

Hiroshi Mori on The gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein induces apoptosis via Tip60 in H4 cells.

COMMENT This nice paper evokes another question and mechanism on Abeta and APP-CT whether toxic Aβ affects APP to enhance the production of APP-C58 as a downstream effector. 0 mori

Benjamin Wolozin on Degradation of the Alzheimer's amyloid beta peptide by endothelin-converting enzyme.

COMMENT "A novel mechanism for stimulating Abeta aggregation and another potential target for inhibiting Abeta aggregation." 0 bwolozin

Benjamin Wolozin on Immunohistochemical localization of neprilysin in the human cerebral cortex: inverse association with vulnerability to amyloid beta-protein (Abeta) deposition.

COMMENT "Neprilysin is a protease that degrades Ab and is emerging as an important regulator of Ab accumulation. The study of neprilysin represents a novel approach towards understanding Alzheimer’s pathophysiology, and understanding its biology represents a