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Background Over 70 million Americans inherit the strongest genetic risk factor for Alzheimer’s disease (AD), apolipoprotein E4 (APOE4), but have no course for reducing their risk. The association of non-steroidal anti-inflammatory drug (NSAID) use with reduced risk of AD for APOE4-carriers suggests that NSAIDs may be useful in AD prevention. Methods We identified phenotypes associated with APOE4 in APOE knock-in mice in order to define modifiable measures that correlate with risk of AD. Results APOE4 mouse brains showed altered post-translational modifications and biochemical distribution of APOE compared to APOE3 mice; these differences were also observed in brains of human APOE4 carriers. Two-month treatment with ibuprofen significantly altered the expression pattern of APOE in APOE4 mice to that of APOE3 mice; PPAR-γ agonist pioglitazone also had a significant effect. APOE4 mice also show deficits in dendritic spine density, and ibuprofen and pioglitazone significantly increased dendritic spine density. Conclusions We report new phenotypes associated with APOE4 in control human and APOE knock-in mice and their mitigation with NSAID treatment, through COX-2 inhibition and PPAR-γ activation.

The utility of Thoracic EndoVascular Aortic Repair (TEVAR) continues to progress at a very rapid rate. Initially implemented for the treatment of thoracic aortic aneurysms, TEVAR has evolved to treat a variety of aortic pathologies and reduce overall morbidity and mortality rates compared with traditional open surgical repair.Given the rapidly evolving nature of endovascular thoracic intervention, we hereby briefly review the current literature on the evolving applications of TEVAR.TEVAR continues to rapidly evolve and is being applied to a growing number of aortic pathologies. Given the perioperative, short- and mid-term morbidity and mortality rates, TEVAR is quickly surpassing traditional open surgical intervention as the ideal procedure for patients undergoing intervention of the descending thoracic aorta and applicability to ascending and arch pathologies is being explored. However, as more data becomes available TEVAR may be associated with higher rates of reoperative requirements. Data remains limited on the long-term efficacy of the intervention and should continue to be investigated.

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