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P3‐296: Assessment of human apolipoprotein E and Aβ clearance rate in vivo through use of stable isotope‐labeling and tandem mass spectrometry
Author(s) -
Kim Jungsu,
Basak Jacob,
Wildsmith Kristin R.,
Jiang Hong,
Mawuenyega Kwasi G.,
Bateman Randall J.,
Parsadanian Maia,
Holtzman David M.
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1864
Subject(s) - apolipoprotein e , in vivo , chemistry , endocrinology , hippocampus , medicine , tandem mass spectrometry , cerebral cortex , biology , mass spectrometry , chromatography , microbiology and biotechnology , disease
ability to promote neuronal repair and plasticity, in contrast to the APOE2 and APOE3 alleles which play a critical role in promotion of remodelling and repair of neurons. We hypothesised that there would be APOE genotype differences in hippocampal neurogenesis which may additionally contribute to APOE genotype differences in repair and plasticity within the adult CNS. Methods: We investigated this using bromodeoxyuridine (BrdU) labelling, which labels newly dividing cells in parallel with doublecortin (DCX) immunohistochemistry to label immature neurons. Young male 3-4 month old wild type C57Bl/J6 (n 11), APOE knockout (APOE KO, n 11), human APOE3 transgenic (n 7) and human APOE4 transgenic mice (n 5) and aged, 15 month old wild-type (n 2), APOE KO (n 8), APOE3 (n 2) and APOE4 (n 3) mice were injected daily with BrDU for 3 days, then sacrificed and brains processed for immunohistochemistry using antibodies to BrdU and DCX and the number of labelled cells quantified within the dentate gyrus. Results: There was no significant difference in the number of cells in the dentate gyrus of young and old wild-type and APOE mice. The number of BrdU and DCX-positive cells were significantly decreased in young APOE KO mice compared with wild type mice (p 0.0001). Although there was no significant difference in the number of BrdU labelled cells between the different APOE genotypes, there was a trend towards increased numbers of DCX cells in APOE3 compared with APOE KO and APOE4 mice. There was a significant decrease in the numbers of BrdU and DCX cells in the brains of aged wild-type, APOE KO, APOE3 and APOE4 mice when compared with young adult mice of the same genotype (p 0.01). There was no significant difference in the numbers of BrdU and DCX cells in the different APOE genotypes of the aged mice. Conclusions: These data suggest that APOE is critical for promoting neurogenesis in the dentate gyrus, and provides some evidence that the APOE3 isoform is more effective than the APOE4 isoform. In addition, the aged brain has an impaired capacity for neurogenesis that was independent of APOE genotype.