Journal of Alzheimer's Disease
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Home > Early in vivo Effects of the Human Mutant Amyloid-β Protein Precursor (hAβPPSwInd) on the Mouse Olfactory Bulb.

TitleEarly in vivo Effects of the Human Mutant Amyloid-β Protein Precursor (hAβPPSwInd) on the Mouse Olfactory Bulb.
Publication TypeJournal Article
Year of Publication2016
AuthorsRusznák, Z, Kim, WScott, Hsiao, J-HT, Halliday, GM, Paxinos, G, Fu, YH
JournalJ Alzheimers Dis
Volume49
Issue2
Pagination443-57
Date Published2016
ISSN1875-8908
KeywordsAge Factors, Alzheimer Disease, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Cell Proliferation, Disease Models, Animal, Gene Expression Regulation, Humans, Ki-67 Antigen, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Nerve Tissue Proteins, Neurogenesis, Neurons, Olfactory Bulb, Piriform Cortex
Abstract

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.

DOI10.3233/JAD-150368
Alternate JournalJ. Alzheimers Dis.
PubMed ID26484907
Grant List1U01MH105971-01 / MH / NIMH NIH HHS / United States
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Source URL: https://www.j-alz.com/content/early-vivo-effects-human-mutant-amyloid-%CE%B2-protein-precursor-ha%CE%B2ppswind-mouse-olfactory-bulb