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P2–416: Expression of human apolipoprotein E‐ε4 reduces uptake and accumulation of docosahexaenoic acid in the brains of mice
Author(s) -
DalPan Alexandre,
Vandal Milene,
Alata Wael,
RiouxPerreault Christine,
Tremblay Cyntia,
Calon Frederic,
Plourde Melanie
Publication year - 2013
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.2013.05.1066
Subject(s) - docosahexaenoic acid , apolipoprotein e , polyunsaturated fatty acid , endocrinology , medicine , biology , apolipoprotein b , fatty acid , biochemistry , disease , cholesterol
experimental and control animals were assessed in Y-maze. Results: Immunizations withWTand P301L-tau proteins induced strong antibody titers (up to 1:50,000 endpoint titers) in rTg4510 mice. Production of IFNg and T-cell proliferation was increased in splenocytes and no T-cell infiltration was observed in the brain. Further IHC analysis of brain tissue showed a significant decrease of total tau levels (H150) in the WT-immunized mice (p<0.05) and a trend toward decrease in the P301L immunized group when compared to controls. Additionally, levels of pS199/202 tau were significantly decreased (p<0.001) after immunization with both tau variants. By Western Blot analysis we observed significant reduction in total tau levels in WT (p<0.01) and P301L (p<0.05) immunized groups. Analysis with paired helical filament-1 (PHF1) antibody demonstrated a significant decrease of tau aggregates in the P301L (p<0.01) but not WT-immunized rTg4510 mice when compared to controls. Y-maze test revealed a transgene effect between ntg and transgenic cohorts (p<0.001), but no rescue by immunization. Further analysis of insoluble tau in the brain and the degree of the brain inflammatory status is ongoing. Conclusions: Our data demonstrate that active tau immunization resulted in robust antibody titters for both WTand P301L-tau proteins and reduced tau pathology in the brain.