Paul Coleman on Parkinson's disease mimicking senile dementia of the Alzheimer type: a clinicopathological study of four autopsy cases.

COMMENT Are these examples of mimicking or of co-morbidity? 0 Paul_Coleman

Bart De Strooper on Presenilin—Guilty of Proteolysis by Association?

COMMENT presenilin-deficient fibroblasts, in addition to the comments from Todd and Mike. The more interesting questions now

Benjamin Wolozin on Another Not-Quite-Parkinson's Model

COMMENT Giasson et al., 2002, see previous comments. Lee observed that only mice expressing the A53T a-synuclein

Todd E. Golde on Presenilin—Guilty of Proteolysis by Association?

COMMENT In a collaboration initiated by Chris Ponting, we have also identified the family of proteins identified by Bruno Martoglio and colleagues (Ponting et al. 2000) [1]. In that paper we speculated that these presenilin homologs (PSH), as we called them, were

Elena Cattaneo on Mutant Huntingtin Linked to Mitochondrial Dysfunction

COMMENT The paper by Panov et al. is absolutely timely. We knew that the mitochondria were involved in HD. We had beautiful evidence that, i.e. animals exposed to systemic injection of a mitochondrial toxin (3-nitropropionic acid) were reproducing neurological de

Fred Van Leuven on Alpha2-macroglobulin deletion polymorphism and plasma levels in late onset Alzheimer's disease.

COMMENT The AD- A2M-connection is too weak to allow the statement as "involved in AD susceptibility" (abstract line 3). In addition, it must be stressed and remembered that A2M is indeed a pan-proteinase inhibitor, but NOT an acute-phase reactant in hum

Carl Cotman on Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis.

COMMENT Context of the study. A major question in the study of brain aging and dementia is: what insults initiate the cascade of pathology causing cognitive dysfunction and the emergence of brain pathology? The candidates are many but two central ones are β-amylo

Benjamin Wolozin on Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) binds the cytoplasmic domain of the Alzheimer's beta-amyloid precursor protein (APP).

COMMENT Despite the dominance of the amyloid hypothesis of Alzheimer's disease, understanding the function of APP and its role in apoptosis remains an important avenue of research. This article describes an important new line of evidence that could explain p

Edward Koo on Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) binds the cytoplasmic domain of the Alzheimer's beta-amyloid precursor protein (APP).

COMMENT Three studies on the app-jip interaction. What does this do? 0 edkoo

Benjamin Wolozin on Distinct FTDP-17 missense mutations in tau produce tau aggregates and other pathological phenotypes in transfected CHO cells.

COMMENT "Important model of aggregation." 0 bwolozin

Benjamin Wolozin on Increased neuronal damage and apoE immunoreactivity in human apolipoprotein E, E4 isoform-specific, transgenic mice after global cerebral ischaemia.

COMMENT This supports the idea that ApoE4 renders some neurons more vulnerable to damage in general. 0 bwolozin

Benjamin Wolozin on Neuronal polo-like kinase in Alzheimer disease indicates cell cycle changes.

COMMENT "This is a very interesting study supporting the hypothesis that cell cycle proteins change in AD." 0 bwolozin

Benjamin Wolozin on A loss of function mutant of the presenilin homologue SEL-12 undergoes aberrant endoproteolysis in Caenorhabditis elegans and increases abeta 42 generation in human cells.

COMMENT "Interesting insights into PS1 action and Ab production." 0 bwolozin

Benjamin Wolozin on Post-translational processing of beta-secretase (beta-amyloid-converting enzyme) and its ectodomain shedding. The pro- and transmembrane/cytosolic domains affect its cellular activity and amyloid-beta production.

COMMENT "BACE appears to be a key therapeutic target in AD." 0 bwolozin

Benjamin Wolozin on Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer's disease.

COMMENT "Our understanding of a-synuclein pathology is limited and increasing daily. This suggests further subdivisions within AD." 0 bwolozin