HOBBS, S.L.; TSAI, P.-S.; NORRIS, D.O.: Cloning of a Partial Sequence of Kokanee Salmon Presenilin-1

Insoluble protein deposits of beta amyloid (A-beta) are one of two brain pathological markers used to diagnosis Alzheimer’s Disease (AD). Mutations in the human presenilin (PS) genes, primarily PS1, result in increased A-beta production and account for the majority of early onset AD. As part of our investigation of the possible role of cortisol in brain aging and neurodegeneration in kokanee salmon (Oncorhynchus nerka kennerlyi), we attempted to clone the PS1 gene in kokanee, which spontaneously exhibit A-beta plaques and accelerated neurodegeneration during spawning. Using degenerate primers against highly conserved regions of PS1, we amplified, from the kokanee brain cDNA, a 374 bp fragment that is highly homologous to the transmembrane regions 2-5 of the human PS1. The obtained kokanee sequence is 77% identical to a corresponding region of the published sequence for human PS1 and 97% to that for zebrafish. The salmon PS1 partial sequence, however, does not bear any of the published sequence variations known to cause AD in humans. Complete sequencing of kokanee PS1 will allow comparison of kokanee and human PS1 genes and permit molecular characterization of kokanee PS1 mRNA expression during spontaneous A-beta plaque formation and accelerated neurodegeneration. Brain PS1 mRNA expression, A-beta plaque formation and neurodegeneration will ultimately serve as endpoints for observing the effects of treating immature kokanee salmon with spawning levels of cortisol. We believe that these studies will lead to the refinement of a novel, non-transgenic model of A-beta plaque formation and accelerated neurodegeneration with implications for human brain aging and AD.