P3–347: Brain derived neurotrophic factor (BDNF) mRNA expression is reduced in postmortem hippocampal dentate gyrus in Alzheimer's disease and dementia with lewy bodies

disease pathology. Inflammatory mediators were recently identified as potent modulators of neurogenesis. Interestingly, Alzheimer’s disease patients have a higher level of neurogenesis than non-demented individuals (Jin K, 2004); however reports from Alzheimer’s disease mouse models are controversial. Molecular modulators of neurogenesis in Alzheimer’s disease are still unknown. Objective(s): 1. Identify the inflammatory mediators released in aging TgCRND8 mice and wildtype littermates. 2. Identify the level of neurogenesis in aging TgCRND8 mice compared to wild-type littermates and evaluate the impact of highly expressed inflammatory mediator(s) on neurogenesis. Methods and Results: Evaluation of the inflammatory profile of 2-18 month-old TgCRND8 and wild-type mice using RNAse protection assay revealed a significant increase in TGF 1 in 14 and 18 month-old in the cortex and the hippocampus of the TgCRND8 mice, but not in the cerebellum. The levels of pro-inflammatory molecules such as IL-1 , TNF-alpha and IL-6 did not differ between transgenic and wild-type mice at any age. Neurogenesis was measured using BrdU incorporation. BrdU-positive cells were approximately 40% higher in the dentate gyrus of young (6 weeks) and old (14 months) TgCRND8 mice when compared to wild-type mice. Double staining revealed that most of the BrdU-positive cells co-localized with doublecortin a marker for immature neurons. Furthermore, the use of an endogenous marker of cell proliferation ki67 confirmed the increase in cell proliferation in the TgCRND8. The importance of the cytokine TGF 1 will be assessed on the on the neurogenesis level observed in the TgCRND8 mice. Conclusions: The TgCRND8 mouse recapitulates features observed in Alzheimer’s disease patients as TGF 1 and neurogenesis levels are increased.