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P4‐040: Memory Self‐appraisal and Pet of Brain Amyloid and Tau in Persons Without Dementia
Author(s) -
Merrill David A.,
Siddarth Prabha,
Ercoli Linda M.,
Burggren Alison C.,
Kepe Vladimir,
Kim Jeanne,
Lavretsky Helen,
Huang S.-C.,
Bookheimer Susan,
Barrio Jorge R.,
Small Gary W.
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.2010.08.100
Subject(s) - dementia , psychology , hippocampal formation , senile plaques , alzheimer's disease , pittsburgh compound b , forgetting , posterior cingulate , neuroscience , medicine , audiology , cortex (anatomy) , disease , cognitive psychology
burden, both SDS soluble and insoluble, in the brain of APP/PS1 mice. No significant changes were observed in the levels of full-length APP, alphaor beta-C-terminal fragments; however, TBHQ significantly increased plasma Ab level, suggesting that TBHQ decreases brain Ab burden not by decreasing APP production or altering the processing of APP through aor b-secretases but probably by increasing excretion of Ab from the brain. PAI-1 is a physiological inhibitor of tPA and uPA, which converts plasminogen into plasmin, a serum protease playing an important role in Ab degradation. We showed previously that PAI-1 protein level was increased in the brain of APP/PS1 transgenic mice and in AD patients while knockout of the PAI-1 gene reduced Ab burden in APP/PS1 mice. Here we further showed that TBHQ treatment significantly reduced PAI-1 protein level in the brain of APP/PS1 mice, accompanied by an increase in tPA activity. Conclusions: Together the data suggest that TBHQ treatment reduces brain Ab burden in APP/PS1mice probably by inhibiting PAI-1 gene expression, which leads to increasedAb degradation through plasmin, and by increasing excretion of Ab from the brain. These results suggest a therapeutic value of TBHQ in the treatment of AD.