Explaining the cause of the amyloid burden in Alzheimer disease.
Arch Neurol. 2002 Sep;59(9):1367-8.
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This manuscript is very similar to ours, which we submitted to a major journal, where it has been held for more than 9 months! Anyway, the results are very interesting. They are consistent with and support our recent discovery made in collaboration with Martin Citron of Amgen, Riqian Yan of Pharmacia, Weiming Xia of the Center for Neurologic Diseases at Harvard Medical School, and Philip Wong and Don Price from Johns Hopkins University. This past February, we reported these findings at a Keystone symposium.
We used our recently developed BACE ELISA to detect significantly elevated BACE levels in our rapidly autopsied brain tissues (i.e. within 3 hours) from Alzheimer's disease patients. Not only that, we also found BACE activity is increased in those sporadic AD brains. Lastly, we found the BACE product, C99, is increased in AD brains compared to non-demented brains. This finding suggests that elevated BACE cleavage of AβPP may be one of the mechanisms that lead to enhanced deposition of amyloid plaques found in brains of sporadic AD patients. Now the question is why BACE is elevated in AD brains. Our groups and many other laboratories are actively working in this direction to see if we will be able to regulate BACE expression and activity in the brain so that we might provide clues for drug discovery.
I highly recommend this article BUT suggest readers to supplement unipolar viewpoint of Archives of Neurology Editor-in-Chief: Alzheimer's disease and amyloid beta protein Koudinov AR et al. Science online, Published 25 June 2002; Amyloid hypothesis: summer 2002 and 8th International Conference on Alzheimer’s disease update. Koudinov and Koudinova BMJ 31 July 2002; The state versus amyloid-beta: the trial of the most wanted criminal in Alzheimer disease. Rottkamp CA et al., 2002; Alzheimer's disease and amyloid beta protein: a dogma is bad for science. Koudinov AR et al. 32nd SFN Annual Meeting November 2-7, 2002 [Abstracts].
Rottkamp CA, Atwood CS, Joseph JA, Nunomura A, Perry G, Smith MA.
The state versus amyloid-beta: the trial of the most wanted criminal in Alzheimer disease.
Peptides. 2002 Jul;23(7):1333-41.
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