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O5‐07‐01: BASELINE FINDINGS FROM GERAS‐US: A LONGITUDINAL COHORT STUDY OF RESOURCE USE AND COSTS OF MILD COGNITIVE IMPAIRMENT AND MILD DEMENTIA DUE TO ALZHEIMER'S DISEASE (AD) IN THE UNITED STATES
Author(s) -
Robinson Rebecca L.,
Rentz Dorene M.,
Bruemmer Valerie,
Andrews Jeffrey Scott,
Zagar Anthony,
Schwartz Ronald L.,
Ye Wenyu,
Fillit Howard M.
Publication year - 2018
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.2018.06.3031
Subject(s) - medicine , dementia , depression (economics) , quality of life (healthcare) , disease , cohort , cognitive impairment , longitudinal study , cognition , gerontology , psychiatry , pathology , nursing , economics , macroeconomics
and spatial memory were assessed using the Novel Object Recognition (NOR) and Novel Location Recognition (NLR) testing paradigms, respectively, both preand end-study. Levels of sirtuin 1 and soluble amyloid precursor protein alpha (sAPPa) were determined in hippocampi and frontal cortices of all mice using custom AlphaLISAs (Perkin-Elmer), and amyloid-beta (Ab) 1-40 and 1-42 were determined by ELISA (Thermo). Results:A03 was found to be orally available and brain-penetrant, and 56-day oral treatment significantly increased SirT1 in the hippocampi of E4FAD mice as compared to vehicle-treated E4FAD mice. A03 treatment of E4FAD mice also improved working object memory in NOR (novelty preference) significantly as compared to E4FAD vehicle-treated controls. Conclusions: A03 is the first small molecule compound found to increase SirT1 in hippocampi of mice wherein huApoE4 and mutated huAPP and huPS1 are expressed. Furthermore, the SirT1 increase was associated with improved cognitive performance. Enhancement of neuroprotective SirT1 in subjects expressing ApoE4 may provide a new therapeutic approach to preventing the onset or slowing/arresting progression of Mild Cognitive Impairment (MCI) or AD in those at high risk for development of these neurodegenerative conditions.