Expression of the amyloid protein precursor of Alzheimer's disease in the developing rat olfactory system

Abstract

The expression of the amyloid protein precursor (APP) of Alzheimer's disease (AD) was examined in the olfactory system of the developing rat. Two monoclonal antibodies were used to detect APP: Alz-90, which specifically recognizes APP, and 22C11 which recognizes both APP and the structurally related protein APLP-2. Very similar patterns of immunoreactivity were observed with both antibodies. APP immunoreactivity was first detected in a subpopulation of olfactory epithelial cells at embryonic day 16 (E16), at a time when primary sensory olfactory axons are first beginning to pierce the glia limitans of the olfactory bulb. At E16, there were more olfactory receptor neurons which expressed APP than the olfactory marker protein (OMP), indicating that some APP-containing neurons were not fully mature. Between E16 and postnatal day 8 (P8), there was a marked increase in the number of primary sensory olfactory neurons expressing APP. In the olfactory bulb, APP was first detected in the mitral cell layer at E18, at a time when synapses are first beginning to form between the dendrites of these cells and primary sensory axons. The level of APP detected within mitral cell perikarya decreased after birth and could no longer be detected between P3 and P8. This indicated that once synaptic connections had been initiated within olfactory glomeruli, the expression of APP within the mitral cells was down-regulated. High levels of APP were, however, detected within the olfactory nerve fiber layer and glomeruli between P3 and P8. The results demonstrate that APP expression in the olfactory system is coordinately regulated with the major periods of synaptogenesis. Since APP is a known neurite outgrowth promoting molecule, we suspect that it may play an important regulatory role in terminal sprouting during synaptogenesis in the olfactory bulb.