Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 49, Issue 2, Pages 443-457Publisher
IOS PRESS
DOI: 10.3233/JAD-150368
Keywords
Alzheimer's disease; amyloid-beta; olfactory bulb; neuronal number; proliferation; neurogenesis
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Funding
- National Health and Medical Research Council Project Grants [NHMRC APP1086643, APP1086083]
- Australian Research Council Centre of Excellence for Integrative Brain Function (ARC Centre Grant) [CE140100007]
- National Institute of Mental Health of the National Institutes of Health [1U01MH105971-01]
- NHMRC Senior Principal Research Fellows [NHMRC APP1043626, APP1079679]
- NATIONAL INSTITUTE OF MENTAL HEALTH [U01MH105971] Funding Source: NIH RePORTER
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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.
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