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. β-Amyloid (Aβ)-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 Aβ 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 Aβ 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., Béréziat, G., Kanony-Truc, C., Clerc, T., Blaise, R., Limon, I. Cerebrovascular β-amyloid deposition and associated microhemorrhages in a Tg2576 Alzheimer mouse model are reduced with a DHA-enriched diet.

The cerebral arterial circle (circulus arteriosus cerebri) or circle of Willis (CoW) is a circulatory anastomosis surrounding the optic chiasma and hypothalamus that supplies blood to the brain and surrounding structures. It has been implicated in several cerebrovascular disorders, including cerebral amyloid angiopathy (CAA)-associated vasculopathies, intracranial atherosclerosis and intracranial aneurysms. Studies of the molecular mechanisms underlying these diseases for the identification of novel drug targets for their prevention require animal models. Some of these models may be transgenic, whereas others will involve isolation of the cerebro-vasculature, including the CoW.The method described here is suitable for CoW isolation in any mouse lineage and has considerable potential for screening (expression of genes, protein production, posttranslational protein modifications, secretome analysis, etc.) studies on the large vessels of the mouse cerebro-vasculature. It can also be used for ex vivo studies, by adapting the organ bath system developed for isolated mouse olfactory arteries.

The cerebral arterial circle (circulus arteriosus cerebri) or circle of Willis (CoW) is a circulatory anastomosis surrounding the optic chiasma and hypothalamus that supplies blood to the brain and surrounding structures. It has been implicated in several cerebrovascular disorders, including cerebral amyloid angiopathy (CAA)-associated vasculopathies, intracranial atherosclerosis and intracranial aneurysms. Studies of the molecular mechanisms underlying these diseases for the identification of novel drug targets for their prevention require animal models. Some of these models may be transgenic, whereas others will involve isolation of the cerebro-vasculature, including the CoW.The method described here is suitable for CoW isolation in any mouse lineage and has considerable potential for screening (expression of genes, protein production, posttranslational protein modifications, secretome analysis, etc.) studies on the large vessels of the mouse cerebro-vasculature. It can also be used for ex vivo studies, by adapting the organ bath system developed for isolated mouse olfactory arteries.