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S2‐01‐02: Tau vaccine: Active immunization with misfolded tau protein attenuates tau pathology in the transgenic rat model of tauopathy
Author(s) -
Novak Michal
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.05.246
Subject(s) - tauopathy , tau protein , transgene , genetically modified mouse , western blot , hyperphosphorylation , immunization , biology , active immunization , pathology , phosphorylation , neuroscience , alzheimer's disease , immunology , medicine , microbiology and biotechnology , disease , antibody , neurodegeneration , biochemistry , gene
perphosphorylated tau in the spinal cord and brain of JNPL3 mice and in AD brain. Results: A significant higher number of contacts between rough endoplasmic reticulum (RER) membranes and mitochondria was observed in motor neurons of the spinal cord in JNLP3 mice than in wild-type mice. This correlated with a preferential increase of the amount of tau at the surface of RER membranes but not at the surface of mitochondria as revealed by tau immunogold labeling in motor neurons where insoluble tau filaments form. Using a subcellular fractionation procedure, an increased amount of phosphorylated tau was noted in the RM (rough microsomes) subfraction where the RER marker, ribophorin was enriched in brain of JNPL3 mice. A similar observation was noted in subfractions isolated from AD brain. The association of hyperphosphorylated tau with ER membranes was confirmed by double immunogold labeling of the subfraction enriched in ER membranes isolated from AD brain. Conclusions: The interaction between RER/mitochondria regulates calcium homeostasis which is perturbed in AD. The present study suggests that the increased number of contacts between RER membranes and mitochondria that could result from the accumulation of tau at the surface of RER membranes might contribute to tau-induced neurodegeneration by perturbing calcium homeostasis.