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P4‐061: TAU PHOSPHORYLATION PROFILE OF HTAU TRANSGENIC MICE
Author(s) -
Neddens Joerg,
Loeffler Tina,
Temmel Magdalena,
Schilcher Irene,
Amschl David,
Hutter-Paier Birgit
Publication year - 2019
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.2019.06.3721
Subject(s) - phosphorylation , genetically modified mouse , transgene , hippocampus , chemistry , tau protein , tauopathy , in vivo , medicine , endocrinology , alzheimer's disease , biology , biochemistry , disease , neurodegeneration , gene , genetics
Our data suggest that total and ptau in hTau mice progressively increases while insoluble tau does barely change. The strongest increase in phosphorylation compared to non-transgenic littermates could be observed for pSer396/404. hTau transgenic mice are therefore a valuable model to study human phosphorylated tau and to test compounds that are directed against this target. Our results show a progressive increase of soluble total tau, pThr231 and pThr181 while phosphorylation of the same residues does not increase in the insoluble brain fraction. Immunofluorescent labeling revealed an increase in total tau levels in the cortex and hippocampus already at the age of 3 months. Analyzing the same brain regions for pSer202/205 levels, only a slight increase at the age of 3 months but a prominent increase at the age of 12 months was observed. Analysis of pSer396/404 revealed a highly increased phosphorylation already at the age of 3 months that stabilized at this level. To evaluate the phosphorylation profile of tau, 3-15 months old hTau mice were analyzed for total tau, pThr181, pSer202/205, pThr231 and pSer396/404 compared to non-transgenic littermates. Different brain regions were analyzed by immunofluorescent labeling. Additionally brain lysate was analyzed by MSD immunosorbent assay. Alzheimer’s disease is characterized by phosphorylation and aggregation of the microtubule associated protein tau. Reliable in vivo models that mimic tau phosphorylation are needed. The hTau transgenic mouse features expression of human tau combined with a knockout of murine tau and belongs to the best animal models to test compounds directed against human tau. Tau Phosphorylation Profile of hTau Transgenic Mice