Edward Koo on Disturbed activation of endoplasmic reticulum stress transducers by familial Alzheimer's disease-linked presenilin-1 mutations.

COMMENT Still more confusion about the upr and presenilins. Initial defects in upr reported for presenilins not confirmed by Thinakaran lab. 0 edkoo

Benjamin Wolozin on Disturbed activation of endoplasmic reticulum stress transducers by familial Alzheimer's disease-linked presenilin-1 mutations.

COMMENT The ER appears to be a critical site for stress in neurodegenerative diseases. Several of the proteins that are implicated in neurodegenerative disease are present in the ER, and affect ER stress responses. Our understanding of the mechanism by which prot

John Hardy on beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease.

COMMENT A fascinating study which further emphasises the parallels between tau andsynuclein pathobiology: mutations in both genes lead to pathology, haplotypes at both genes predispose to sporadic disease, both pathologies occur 'downstream' in Alzheime

John Hardy on Prion protein protects human neurons against Bax-mediated apoptosis.

COMMENT It will be interesting to see whether doppel antagonises this effect. 0 J.Hardy

Benjamin Wolozin on The amyloid precursor protein (APP)-cytoplasmic fragment generated by gamma-secretase is rapidly degraded but distributes partially in a nuclear fraction of neurones in culture.

COMMENT Recent reports indicate that the C-terminus of APP can stimulate gene transcription. This study provides support for the connection between APP and gene transcription by showing that APP can be observed in the nucleus. 0 bwolozin

Benjamin Wolozin on Proteasome inhibition in glyoxal-treated fibroblasts and resistance of glycated glucose-6-phosphate dehydrogenase to 20 S proteasome degradation in vitro.

COMMENT Increasing evidence focuses attention on proteasomal inhibition in neurodegeneration. Many protein aggregates have been shown to inhibit proteasomal activity, and inhibiting proteasomal activity is toxic to cells. This report now expands the types of prot

Benjamin Wolozin on Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-D-glucose/poitron-emission tomography (FDG/PET).

COMMENT Being able to predict cognitive decline has been one of the great challenges in the field of Alzheimer's disease. This study provides a potentially important method for establishing predictive paradigms. 0 bwolozin

Benjamin Wolozin on Immunization with a nontoxic/nonfibrillar amyloid-beta homologous peptide reduces Alzheimer's disease-associated pathology in transgenic mice.

COMMENT This provides further confirmation of the value of immunization in reducing amyloid burden. 0 bwolozin

Gabrielle Strobel on Molecular changes of preclinical scrapie can be detected by infrared spectroscopy.

COMMENT Q & A with Gabrielle Strobel, ARF, and Dieter Nauman, Robert Koch Institute, Berlin. Q: Could this technique be developed to detect early pathological changes in Alzheimer Disease? Can it pick up low-molecular weight protein aggregates? A: Our diagnos

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

COMMENT Seminal studies of LeBlanc (1995) have shown that primary neurons committed to undergo apoptosis by serum-deprivation produced increased amount of Abeta. These findings have been confirmed in cerebellar granule cells (Galli et al., 1998), in retinoic acid

Peter Davies on Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local beta-structure.

COMMENT "This paper continues the Mandelkow's fine work trying to unravel the mechanism of PHF formation by in vitro studies of structural changes that occur in tau on aggregation. Their identification of regions of tau that seem to be important for agg

Jorge Barrio on Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease.

COMMENT "As indicated in our paper (Shoghi-Jadid et al, 2002), we agree with Dr. Klunk's point that additional study of our new amyloid-binding agent is needed. Clearly, no single publication could have addressed all the additional areas that need to be

Benjamin Wolozin on Nicastrin binds to membrane-tethered Notch.

COMMENT This is an interesting paper that brings together Nicastrin and Notch, which complements the previous association of presenilin and Notch. 0 bwolozin

Chris Exley on Notch Pathway Implicated in Multiple Sclerosis

COMMENT The two recent papers published in Science showing an apparent connection between A beta and tau pathologies in transgenic mice models are interesting. However, neither paper reports the effect of a positive control. In both cases a combination of two pos

John Hardy on A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease.

COMMENT An extremely important paper which provides the experimental evidence that cholesterol lowering drugs may be beneficial to Alzheimer's disease..... while this paper does not use statins, the treatment implications are clear. From a basic science pers