THE RELATIONSHIP OF TAU PATHOLOGY AND EXTRACELLULAR TAU IN THE BRAINS OF TG4510 MICE

The accumulation of tau protein into neurofibrillary tangles, composed of hyperphosphorylated aggregated Tau, is a pathological hallmark in Alzheimer’s disease (AD) and tauopathies. Total and phosphorylated tau in the cerebrospinal fluid (CSF) is used as surrogate biomarker of tau in the brain. However, it is unclear how the CSF tau relates to tau pathology and extracellular tau in the brain. In our previous study in Tg4510 mice, we observed a strong correlation between levels of CSF Tau and levels of brain insoluble Tau before significant brain atrophy arises. In this study, we developed microdialysis technique to sample extracellular fluid (eCF) in the brain and intended to further investigate the relationship among changes in insoluble Tau, eCF tau and CSF Tau in the Tg4510 mice. For push-pull microdialysis, dialysis probes were placed in the hippocampus of Tg4510 mice. eCF was collected, followed by collection of CSF and brain (including cortex and hippocampus) in the same mouse. AT8 ELISA was used to measure the levels of hyperphosphorylated insoluble tau in P1 fractions of the brain. We have developed ELISA to measure Tau that encompasses the N-terminus, mid-portion or C-terminus of tau. In both eCF and CSF, we observed that N-terminus-containing Tau may be more sensitive to be detected than full-length Tau. We are analyzing the relationship of tau in three compartments, i.e. brain parenchyma, eCF and CSF, of Tg4510 mice brain. The results will be presented at the conference.