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P3‐246: Drastic impact on Abeta accumulation in APP Tg mice by genetic background
Author(s) -
Morihara Takashi,
Kudo Takashi,
Hayashi Noriyuki,
Kamino Kojin,
Takeda Masatoshi
Publication year - 2008
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.2008.05.1813
Subject(s) - ratón , microbiology and biotechnology , immunology , medicine , biology
Background: Though a great deal of effort has been made on the searching for the risk genes of Alzheimer disease (AD), there is little success, except ApoE. Animal model has many advantages (strict control of environmental factors, direct measurement of amyloid pathology, etc) compared to human studies. Methods: APP Tg mice (Tg2576) which are usually maintained by B6/SJL hybrid mice were crossed onto C57BL6/J, SJL/J and DBA2/J inbred strains. The levels of Abeta40 and Abeta42 in Triton and GuHCl fraction from cortex were measured by ELISA. Results: The shortened life span were observed in APP Tg mice with B6 rich genetic background (B6 75%, SJL 25%), which was similar to previous report (Carlson Hum Mol Genet 1997). No significant life span change, however, was observed in the mice with either SJL or DBA rich genetic background. Analysis of 59 APP Tg mice at the age of 12 months showed that lower Abeta accumulation in mice with DBA rich genetic background compared to SJL or B6 rich genetic background. For example, significant difference (p 0.01, Turkey-Kramer) were observed in Abeta40 (-82%) and Abeta42 (-68%) levels in Triton fraction between SJL 84% B6 16% mice and DBA 75% B6 16% SJL 9% mice. Drastic difference (p 0.01, TurkeyKramer) were observed in Abeta40 and Abeta42 levels also from GuHCl fraction between SJL 69% B6 31% and DBA 75% B6 16% SJL 9% mice (-85% and -68%) and between SJL 69% B6 31% and DBA 50% B6 31% SJL 19% mice (-75% and -50%). We focus on SJL and DBA, because the difference of Abeta accumulation was most drastic and both genetic backgrounds have no impact on life span. More animals are being analyzed and amyloid pathology modifier candidate genes will be searched using arrays. Conclusions: Our data demonstrated that genetic background impact on amyloid pathology in APP Tg mice. Mice model can be a useful tools to discover risk genes for human AD.