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O3‐07‐01: Oral health and dementia: Current evidence and recommendations
Author(s) -
Shuman Stephen K.,
Simonson Peggy J.
Publication year - 2015
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.2015.07.273
Subject(s) - dementia , medicine , tooth loss , oral health , health care , gerontology , population , disease , family medicine , environmental health , pathology , economics , economic growth
AD risk for those identified with the APOE4 allele. Methods:Using an APOE knock-in mouse model, we sought to identify differences in brain biochemistry accompanying the APOE risk genotype (APOE4 mice) compared to the absence of this risk factor (APOE3 mice). Results:APOE4 mice had significantly more APOE in Tris buffered saline(TBS-) relative to TBS with triton X (TBSX)-soluble brain fractions, and a threefold higher level of brain ABCA1, compared to APOE3 mice. APOE4 mice also had impaired spatial memory and reduced dendritic spine density in the entorhinal cortex compared to APOE3 mice, as we had previously reported. These measures provided tractable, novel targets for analyzing compounds to reduce APOE-associated effects in the brain. Epidemiological studies repeatedly found non-steroidal anti-inflammatory drugs (NSAIDs) reduce AD risk, and we tested whether one such NSAID, ibuprofen, affected these newly identified APOEassociated biomarkers in mice. Two months of ibuprofen significantly shifted the distribution of APOE and ABCA1 levels to the patterns seen in APOE3 mice. Ibuprofen also rescued spatial learning deficits and dendritic spine density in 6-month-old APOE4 mice. Conclusions:These studies indicate ibuprofen significantly reduces differences in three measures between normal APOE3 and APOE4 mice, which could serve as biomarkers for increased AD risk associated with the APOE4 risk factor. We are currently investigating whether other NSAIDs have similar effects on these biomarkers of APOE4 to determine the molecular mechanism of their protective effects.