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- W2033596411 abstract "Gamma-secretase mediated processing of amyloid precursor protein (APP) results in the generation of Abeta and APP intracellular domain (AICD). Whereas contribution of the Abeta fragments to Alzheimer's disease (AD) pathology are well documented, relatively little is known whether and to what extent AICD also contributes to AD features. We generated AICD transgenic mice and found these mice to recapitulate several features of AD including neurodegeneration. Neuronal loss is an important pathology observed in AD brains and could be contributed by the death of neurons or decreased adult neurogenesis. This study was aimed examining the status of adult neurogenesis in the AICD transgenic mice. We generated transgenic mice coexpressing AICD and Fe65. These mice were injected with BrdU (i.p) and adult neurogenesis in the dentate gyrus was measured by immunohistochemistry. We measured proliferation and maturation of newly generated cells. These experiments were performed in mice at 1.5, 3 or 12 months of age. We find that proliferation of newly generated cells was not different in 1.5 month-old AICD transgenic mice when compared to non-transgenic controls or mice expressing Fe65 alone. However, adult neurogenesis was significantly reduced in 3 month-old AICD transgenic mice. We also observed increased neuroinflammation in these mice indicated by altered cytokine profile and the presence of activated microglia. Impaired neurogenesis was also observed in 12 months mice. Interestingly, maturation or differentiation of newly generated cells was not altered by AICD. Our data show that expression of AICD significantly inhibits adult hippocampal neurogenesis without affecting the maturation of differentiation of the newly generated cells. It has been suggested that adult neurogenesis is impaired in human AD brains some studies have shown decreased neurogenesis in mouse models of AD. Since AICD transgenic mice show reduced adult neurogenesis in addition to several pathological features of AD, these results collectively indicate that AICD could make significant contributions to AD." @default.
- W2033596411 created "2016-06-24" @default.
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- W2033596411 date "2009-07-01" @default.
- W2033596411 modified "2023-09-27" @default.
- W2033596411 title "P4-177: Aberrant adult neurogenesis in transgenic mice expressing APP intracellular domain" @default.
- W2033596411 doi "https://doi.org/10.1016/j.jalz.2009.04.744" @default.
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