Distribution of beta-amyloid and amyloid precursor protein in the brain ofspawning (senescent) salmon: a natural, brain-aging model

Brain amyloid precursor protein (APP), a normal constituent of neurons, gli al cells and cerebrospinal fluid, has several proposed functions (e.g., in neuronal growth and survival). It appears, however, that altered processing of APP is an initial or downstream step in the neuropathology of brain agi ng, Alzheimer's disease (AD), and Down's syndrome (DS). Some studies sugges t that proteolytic cleavage of APP, producing beta-amyloid (A beta(1-42)), could have neurotoxic or neuroprotective effects. In this study, we utilize d antibodies to human APP(695) and A beta(1-42), and Congo red staining, to search for amyloid deposition in the brain of semelparous spawning kokanee salmon (Oncorhynchus nerka kennerlyi). Intracellular APP(695) immunoreacti vity (APP-ir) was observed in brain regions involved in gustation (glomerul osus complex), olfaction (putative hippocampus, olfactory bulb), vision (op tic tectum), the stress response (nucleus preopticus and nucleus lateralis tuberis), reproductive behavior (nucleus preopticus magnocellularis, nucleu s preopticus periventricularis, ventral telencephalon), and coordination (c erebellum). Intra- and extra-neuronal A beta(1-42) immunoreactivity (A beta -ir) were present in all APP-ir regions except the nucleus lateralis tuberi s and Purkinje cells of the cerebellum (coordination). Thus, the relationsh ip between APP and AP deposition during brain aging could shed light on the processing of APP into AP, neurodegeneration, and possible protection of n eurons that are functioning in spawning but senescent salmon. Pacific salmo n, with their predictable and synchronized life history, could provide rese arch options not available with the existing models for studies of brain ag ing and amyloidosis. (C) 2000 Elsevier Science B.V. All rights reserved.