Early in vivo Effects of the Human Mutant Amyloid-β Protein Precursor (hAβPPSwInd) on the Mouse Olfactory Bulb.
The amyloid-β protein precursor (AβPP) has long been linked to Alzheimer's disease (AD). Using J20 mice, which express human AβPP with Swedish and Indiana mutations, we studied early pathological changes in the olfactory bulb. The presence of AβPP/amyloid-β (Aβ) was examined in mice aged 3 months (before the onset of hippocampal Aβ deposition) and over 5 months (when hippocampal Aβ deposits are present). The number of neurons, non-neurons, and proliferating cells was assessed using the isotropic fractionator method. Our results demonstrate that although AβPP is overexpressed in some of the mitral cells, widespread Aβ 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 AβPP; (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) AβPP/Aβ-associated pathological changes that take place in the J20 hippocampus and olfactory bulb are not identical.
Neuroscience Research Australia, Sydney, NSW, Australia.
Zoltán
Z
Rusznák
Neuroscience Research Australia, Sydney, NSW, Australia.|School of Medical Science, The University of New South Wales, Sydney, NSW, Australia.
Woojin Scott
WS
Kim
Neuroscience Research Australia, Sydney, NSW, Australia.|School of Medical Science, The University of New South Wales, Sydney, NSW, Australia.
Jen-Hsiang T
JH
Hsiao
Neuroscience Research Australia, Sydney, NSW, Australia.|School of Medical Science, The University of New South Wales, Sydney, NSW, Australia.
Glenda M
GM
Halliday
Neuroscience Research Australia, Sydney, NSW, Australia.|School of Medical Science, The University of New South Wales, Sydney, NSW, Australia.
George
G
Paxinos
Neuroscience Research Australia, Sydney, NSW, Australia.|School of Medical Science, The University of New South Wales, Sydney, NSW, Australia.
YuHong
Y
Fu
D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009830:Olfactory Bulb / Q000378:metabolism* / Q000473:pathology; D066195:Piriform Cortex / Q000378:metabolism / Q000473:pathology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins
Alzheimer’s disease; amyloid-β; neurogenesis; neuronal number; olfactory bulb; proliferation