Endothelial expression of human amyloid precursor protein leads to amyloid β in the blood and induces cerebral amyloid angiopathy in knock-in mice

The deposition of amyloid β (Aβ) in blood vessels of the brain, known as cerebral amyloid angiopathy (CAA), is observed in most patients with Alzheimer’s disease (AD). Compared with the pathology of CAA in humans, the pathology in most mouse models of AD is not as evident, making it difficult to examine the contribution of CAA to the pathogenesis of AD. On the basis of biochemical analyses that showed blood levels of soluble amyloid precursor protein (APP) in rats and mice were markedly lower than those measured in human samples, we hypothesized that endothelial APP expression would be markedly lower in rodents and subsequently generated mice that specifically express human WT APP (APP770) in endothelial cells (ECs). The resulting EC-APP770⁺ mice exhibited increased levels of serum Aβ and soluble APP, indicating that endothelial APP makes a critical contribution to blood Aβ levels. Even though aged EC-APP770⁺ mice did not exhibit Aβ deposition in the cortical blood vessels, crossing these animals with APP knock-in mice (App^NL-F/NL-F) led to an expanded CAA pathology, as evidenced by increased amounts of amyloid accumulated in the cortical blood vessels. These results highlight an overlooked interplay between neuronal and endothelial APP in brain vascular Aβ deposition. We propose that these EC-APP770⁺:App^NL-F/NL-F mice may be useful to study the basic molecular mechanisms behind the possible breakdown of the blood–brain barrier upon administration of anti-Aβ antibodies.     

O2-stimulated synthesis of bacteriochlorophyll and carotenoids in marine bacteria

We examined the effects of a limitation of the O₂-supply onthe syntheses of bacteriochlorophyll a_p and carotenoids in isolatesof aerobic marine bacteria, OCh 101 and OCh 114, grown heterotrophically.Whereas they formed these pigments fairly well under high aerationin the dark, a limitation of the O₂-supply resulted in the decreasedsyntheses of bacteriochlorophyll in both strains. Synthesesof carotenoids also were depressed under low aeration but toa lesser extent (especially in OCh 101) than the depressionof bacteriochlorophyll synthesis. Aerobic incubation of a cultureof OCh 101, that previously had been grown semiaerobically,induced the supplementary synthesis of bacteriochlorophyll.This induction was inhibited almost completely by chloram-phenicol.The absorption spectra of suspensions and solvent extracts ofcells grown aerobically or semiaerobically are reported. (Received May 30, 1980; )     

Migratory history of Rhinogobius sp. OR morphotype “Shimahire” as revealed by otolith Sr:Ca ratios

The migratory history of the Rhinogobius sp. OR morphotype “Shimahire” collected from a slower current environment in the Maruyama River, the Ibo River, and the Kako River, Japan, was studied by examining the strontium and calcium concentrations in the otoliths. The otolith Sr:Ca ratios of almost all samples showed consistently low ratios from the core to the edge, reflecting the fact that the organisms had been living in a freshwater environment their entire lives. The ratios of Rhinogobius sp. CB and Rhinogobius flumineus living in the sympatric habitats with the Rhinogobius sp. OR morphotype “Shimahire” in the Kako River showed an amphidromous and fluvial life cycle, respectively. These findings suggest that the Rhinogobius sp. OR morphotype “Shimahire” has a freshwater resident life cycle.     

O2-stimulated synthesis of bacteriochlorophyll and carotenoids in marine bacteria

We examined the effects of a limitation of the O₂-supply onthe syntheses of bacteriochlorophyll a_p and carotenoids in isolatesof aerobic marine bacteria, OCh 101 and OCh 114, grown heterotrophically.Whereas they formed these pigments fairly well under high aerationin the dark, a limitation of the O₂-supply resulted in the decreasedsyntheses of bacteriochlorophyll in both strains. Synthesesof carotenoids also were depressed under low aeration but toa lesser extent (especially in OCh 101) than the depressionof bacteriochlorophyll synthesis. Aerobic incubation of a cultureof OCh 101, that previously had been grown semiaerobically,induced the supplementary synthesis of bacteriochlorophyll.This induction was inhibited almost completely by chloram-phenicol.The absorption spectra of suspensions and solvent extracts ofcells grown aerobically or semiaerobically are reported. (Received May 30, 1980; )