Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis

The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for Alzheimer’s disease (AD). The influence of apoE on amyloid β (Aβ) accumulation may be the major mechanism by which apoE affects AD. ApoE interacts with Aβ and facilitates Aβ fibrillogenesis in vitro. In addition, apoE is one of the protein components in plaques. We hypothesized that certain anti-apoE antibodies, similar to certain anti-Aβ antibodies, may have antiamyloidogenic effects by binding to apoE in the plaques and activating microglia-mediated amyloid clearance. To test this hypothesis, we developed several monoclonal anti-apoE antibodies. Among them, we administered HJ6.3 antibody intraperitoneally to 4-mo-old male APPswe/PS1ΔE9 mice weekly for 14 wk. HJ6.3 dramatically decreased amyloid deposition by 60–80% and significantly reduced insoluble Aβ40 and Aβ42 levels. Short-term treatment with HJ6.3 resulted in strong changes in microglial responses around Aβ plaques. Collectively, these results suggest that anti-apoE immunization may represent a novel AD therapeutic strategy and that other proteins involved in Aβ binding and aggregation might also be a target for immunotherapy. Our data also have important broader implications for other amyloidosis. Immunotherapy to proteins tightly associated with misfolded proteins might open up a new treatment option for many protein misfolding diseases

Amber inclusions from New Zealand

Amber is nearly ubiquitous in lignites from Otago and Southland, and elsewhere throughout New Zealand; however, until now no amber inclusions have been reported from these fossil tree resins. We have discovered and examined amber from 22 Cretaceous to Miocene sites in southern New Zealand and recovered inclusions in three localities: Cosy Dell (Late Oligocene), Roxburgh (Early Miocene), and Hyde (Early Miocene). Preparation of New Zealand amber and exposing its inclusions for study under incident and transmitted light is challenging and time-consuming, since most amber samples are brittle and opaque. Thus, we apply epoxy preparation under vacuum before grinding and imaging in order to stabilize the amber lumps and to clear the fossil resin for light-microscopy. To date we have recovered about 63 arthropods, as well as plant remains, fungi, and nematodes. Arachnids include diverse mites from the Mesostigmata, Oribatida, Astigmata, and Prostigmata, a variety of spiders and their web remains with prey, and a pseudoscorpion. Some Collembola were identified as belonging to the family Entomobryidae. Inclusions of insects comprise members of the families Dermestidae (Coleoptera), Mymaridae and Scelionidae (Hymenoptera), Veliidae (Heteroptera), Ceratopogonidae and Mycetophilidae (Diptera) as well as Psocoptera, and Lepidoptera. The most abundant fungi in New Zealand amber are hyphomycetes similar to the genus Casparyotorula from European Palaeogene ambers, and we discovered that such fungi still grow on resin of the extant Agathis australis, the iconic New Zealand kauri. Furthermore, specimens of the genus Metacapnodium (Capnodiales) represent the first southern hemispheric fossils of sooty moulds, a group of saprophytic ascomycetes with brown hyphae, often forming extensive subicula on living plant surfaces. These fungi are ubiquitous and diverse in New Zealand today. Many of the new amber fossils represent groups with an otherwise poor fossil record in the entire Southern Hemisphere. The systematic and ecological diversity of the inclusions highlights the potential of New Zealand amber for reconstructing past terrestrial ecosystems of Zealandia, one of the biogeographically crucial Gondwanan landmasses.Alexander R. Schmidt, Uwe Kaulfuss, Jennifer M. Bannister, Viktor Baranov, Christina Beimforde … John G. Conran … et al

Comparison of sibrafiban with aspirin for prevention of cardiovascular events after acute coronary syndromes: a randomised trial

Item does not contain fulltext15 p