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O4‐02‐06: Regional cerebral glucose metabolism is associated with interstitial fluid Aβ concentration and plaque deposition in Tg2576 mice
Author(s) -
Bero Adam W.,
Stewart Floy R.,
Parsadanian Maia,
Holtzman David M.
Publication year - 2010
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.2010.05.478
Subject(s) - microdialysis , interstitial fluid , chemistry , extracellular , in vivo , amyloid (mycology) , western blot , extracellular fluid , interstitial space , metabolism , endocrinology , medicine , biology , biochemistry , inorganic chemistry , microbiology and biotechnology , gene
the rapid turnover of the endogenous protein in the wild-type mouse. sAPP is cleared from the brain parenchyma more slowly, particularly in the Tg2576 model where the half-life of sAPP is nearly doubled compared to wild-type mice. The important Ab degrading enzymes neprilysin and IDE were found to be highly stable in the brain, and soluble Ab40 and Ab42 levels in both wild-type and Tg2576 mice rapidly declined following the depletion of APP. Conclusions: Our findings unexpectedly show that of these various AD-relevant protein metabolites, sAPP turnover in the brain is the most different when comparing a wild-type mouse and a b-amyloid plaque containing Tg2576 mouse. Given the neurotrophic roles attributed to sAPP, the enhanced stability of sAPP may explain the lack of robust neurodegeneration in the brain of Tg2576 mice despite abundant b-amyloid deposition.