Early in vivo Effects of the Human Mutant Amyloid-β Protein Precursor (hAβPPSwInd) on the Mouse Olfactory Bulb.

The amyloid-beta protein precursor (A beta PP) has long been linked to Alzheimer's disease (AD). Using J20 mice, which express human A beta PP with Swedish and Indiana mutations, we studied early pathological changes in the olfactory bulb. The presence of A beta PP/amyloid-beta (A beta) was examined in mice aged 3 months (before the onset of hippocampal A beta deposition) and over 5 months (when hippocampal A beta deposits are present). The number of neurons, non-neurons, and proliferating cells was assessed using the isotropic fractionator method. Our results demonstrate that although A beta PP is overexpressed in some of the mitral cells, widespread A beta deposition and microglia aggregates are not prevalent in the olfactory bulb. The olfactory bulbs of the younger J20 group harbored significantly fewer neurons than those of the age-matched wild-type mice (5.57 +/- 0.13 million versus 6.59 +/- 0.36 million neurons; p = 0.011). In contrast, the number of proliferating cells was higher in the young J20 than in the wild-type group (i.e., 6617 +/- 425 versus 4455 +/- 623 cells; p = 0.011). A significant increase in neurogenic activity was also observed in the younger J20 olfactory bulb. In conclusion, our results indicate that (1) neurons participating in the mouse olfactory function overexpress A beta PP; (2) the cellular composition of the young J20 olfactory bulb is different from that of wild-type littermates; (3) these differences may reflect altered neurogenic activity and/or delayed development of the J20 olfactory system; and (4) A beta PP/A beta-associated pathological changes that take place in the J20 hippocampus and olfactory bulb are not identical.