| First Author | Hur J | Year | 2018 |
| Journal | FASEB J | Volume | 32 |
| Issue | 9 | Pages | 4972-4983 |
| PubMed ID | 29620941 | Mgi Jnum | J:280599 |
| Mgi Id | MGI:6357116 | Doi | 10.1096/fj.201800200R |
| Citation | Hur J, et al. (2018) Cerebrovascular beta-amyloid deposition and associated microhemorrhages in a Tg2576 Alzheimer mouse model are reduced with a DHA-enriched diet. FASEB J 32(9):4972-4983 |
| abstractText | Cerebral amyloid angiopathy (CAA) is a major contributor to Alzheimer's disease (AD) pathogenesis. Like AD, CAA is often accompanied by marked inflammation, aggravating associated vasculopathies. No evidence-based prevention or treatment strategies are available. Here, we evaluate the possible beneficial effect of a diet enriched with docosahexaenoic acid (DHA), which is known to attenuate inflammation in CAA. Tg2576 mice, a transgenic model of AD/CAA, were fed a DHA-enriched diet starting at 2 mo of age and ending at 10, 14, or 18 mo of age. beta-Amyloid (Abeta)-peptide deposition and bleeding were visualized by immunohistochemistry or histochemistry on coronal sections of the brain. DHA, arachidonic acid, and eicosanoid levels were measured by liquid chromatography/mass spectrometry or GC-MS. DHA-enriched diet throughout aging limits the accumulation of vascular Abeta peptide deposits as well as the likelihood of microhemorrhages. There is a strong correlation between systemic 12-hydroxyeicosatetraenoic acid (HETE) levels and the size of the area affected by both vascular amyloid deposits and hemorrhages. The lowest levels of 12-HETE, a lipid-derived proinflammatory product of 12-lipoxygenase (LOX), were found in DHA-fed mice. In vitro experiments performed on amyloid vascular smooth muscle cells showed that a 12-LOX inhibitor almost completely blocked the Abeta1-40 peptide-induced apoptosis of these cells. This study yet again highlights the important role of inflammation in CAA pathogenesis and identifies potential new targets for preventive care.-Hur, J., Mateo, V., Amalric, N., Babiak, M., Bereziat, G., Kanony-Truc, C., Clerc, T., Blaise, R., Limon, I. Cerebrovascular beta-amyloid deposition and associated microhemorrhages in a Tg2576 Alzheimer mouse model are reduced with a DHA-enriched diet. |
