Intraneuronal amyloid precursor protein (APP) and appearance of extracellular β‐amyloid peptide (aβ) in the brain of aging kokanee salmon

Antibodies to human amyloid precursor protein (APP₆₉₅) and beta‐amyloid peptide (Aβ_1‐42) were used to determine timing of amyloidosis in the brain of kokanee salmon (Oncorhynchus nerka kennerlyi) in one of four reproductive stages: immature (IM), maturing (MA), sexually mature (SM), and spawning (SP), representing a range of aging from somatically mature but sexually immature to spawning and somatic senescence. In IM fish, immunoreactive (ir) intracellular APP occurred in 18 of 23 brain regions. During sexual maturation and aging, the number of neurons expressing APP increased in 11 of these APP‐ir regions. Aβ‐ir was absent in IM fish, present in seven regions in MA fish, moderately abundant in 15 regions in SM fish, and was most abundant in all brain regions of SP fish exhibiting Aβ‐ir. Intracellular APP‐ir was observed in brain regions involved in sensory integration, olfaction, vision, stress responses, reproduction, and coordination. Intra‐ and extracellular Aβ_1‐42 immunoreactivity (Aβ‐ir) was present in all APP‐ir regions except the nucleus lateralis tuberis (hypothalamus) and Purkinje cells (cerebellum). APP‐ir and Aβ deposition increase during aging. APP‐ir is present in IM fish; Aβ‐ir usually appears first in MA or SM fish and increases in SM fish as does APP‐ir. Extracellular Aβ deposition dramatically increases between SM and SP stages (1–2 weeks) in all fish, indicating an extremely rapid and synchronized process. Rapid senescence observed in pacific salmon could make them a useful model to investigate timing of amyloidosis and neurodegeneration during brain aging. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 11–20, 2002