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Refining the kokanee salmon model of vertebrate brain aging and Alzheimer's Disease: progress in cloning the presenilin-1 gene.

Over 85 point mutations in the presenilin genes, PS1 and PS2, are known to cause early onset Alzheimer's Disease with 100% penetrance. PS1 is believed to function as the "gamma secretase" that cleaves amyloid precursor protein to yield beta-Amyloid (A [beta]) peptides. Cerebral A [beta] peptides aggregate into extracellular deposits called plaques, the presence of which is used to diagnose AD. Although most animals used in AD research don't naturally produce A [beta] plaques, kokanee salmon both naturally and invariably produce A [beta] plaques during migration and spawning. We sequenced 374 nucleotides of a putative kokanee PS1 that is 74% identical to transmembrane regions 2-5 of human PS1. The salmon PS1 partial sequence does not bear any of the published sequence variations that are known to cause AD in humans. Complete sequencing of kokanee salmon PS1 will allow comparison of salmon and human PS1 sequences and in-vitro biochemical activity, and also permit characterization by in-situ hybridization of salmon PS1 mRNA expression during spontaneous A [beta] plaque formation and accelerated neurodegeneration. We hope that these studies will lead to the development and use of a novel nontransgenic model of A [beta] plaque formation and accelerated neurodegeneration with implications for human brain aging and AD.

Steven L. Hobbs *, Pei-San Tsai, David O. Norris * EPO Biology, University of Colorado, Boulder.

* Denotes membership in the Colorado-Wyoming Academy of Science.
COPYRIGHT 2002 Colorado-Wyoming Academy of Science
No portion of this article can be reproduced without the express written permission from the copyright holder.
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Author:Hobbs, Steven L.; Tsai, Pei-San; Norris, David O.
Publication:Journal of the Colorado-Wyoming Academy of Science
Article Type:Brief Article
Geographic Code:1USA
Date:Apr 1, 2002
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