Transmission study of Alzheimer pathology using brain microdialysis

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The purpose of this study is to examine the possible roles of soluble Abeta and tau released from neurons into the extracellular space in the transmission of Alzheimer pathology using the brain microdialysis technique. In a preliminary experiment, only very low levels of tau were detected by microdialysis in the hippocampus of our tau transgenic (Tg) mice. To generate a better donor of soluble Abeta and tau, we crossbred our APP Osaka mutant Tg mice and wild-type tau Tg mice. The resultant double Tg mice showed Abeta oligomer accumulation, tau hyperphosphorylation, synapse loss, and memory impairment at 6 months, and neurofibrillary tangle formation and neuronal loss at 18 months in the absence of tau mutations, all of which appeared earlier than in the parent Tg mice. This mouse model would be a useful tool for investigation of the intercellular propagation of amyloid and tau pathologies.