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- W265053018 abstract "A form of the amyloid cascade hypothesis proposes that soluble forms of A[Beta] are the initiating factor of pathogenesis in Alzheimer's disease (AD). A[Beta] is known to alter the structure and function of synapses, and this synaptic malfunction is proposed to underlie the initial memory problems of AD, however it is currently unclear where the A[Beta] induced synaptic dysfunction is initiated. Specifically, is the synaptic toxicity initiated by the pre or post-synaptic neuron. In this project we used triple transgenic mice employing the tet off and cre/loxP systems to direct expression of the Amyloid precursor protein (APP) in the dentate gyrus, CA3 or CA1 regions of the hippocampus. I provided basic characterizations of these three lines of triple transgenic mice, by ensuring the correct spatial location of cre/loxP recombination in the three lines, and by determining the approximate transgenic APP expression per transgenic APP expressing neuron in the three different genotypes. We showed that CA1 and CA3 mice expressed similar levels of APP, while DG mice expressed much less. Our results also showed that A[Beta] derived from the postsynaptic neuron did not cause significant LTP deficit, while presynaptically derived A[Beta] caused an LTP deficit in CA3 mice. Expression of APP in dentate gyrus did not result in LTP deficit in the efferent synapses. However, because APP expression was substantially less in the DG neurons, reduction in DG mice is likely due to lower transgenic APP expression. Treatment with doxycycline or [gamma]-secretase inhibitor to inhibit APP or A[Beta] production, respectively, restored the defects in synaptic plasticity, thus confirming the notion that the LTP impairment is due to A[Beta]. In conclusion, my studies provided strong evidence that A[Beta]-induced synaptic toxicity originated from the pre-synaptic neuron" @default.
- W265053018 created "2016-06-24" @default.
- W265053018 creator A5061027240 @default.
- W265053018 date "2012-01-01" @default.
- W265053018 modified "2023-09-24" @default.
- W265053018 title "Characterization of mice expressing APPSwe/Ind in DG, CA3 or CA1 of the hippocampus" @default.
- W265053018 hasPublicationYear "2012" @default.
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