Prominent and Persistent Extraneural Infection in Human PrP Transgenic Mice Infected with Variant CJD

Background. The evolution of the variant Creutzfeldt-Jakob disease (vCJD) epidemic is hazardous to predict due to uncertainty in ascertaining the prevalence of infection and because the disease might remain asymptomatic or produce an alternate, sporadic-like phenotype. Methodology/Principal Findings. Transgenic mice were produced that overexpress human prion protein with methionine at codon 129, the only allele found so far in vCJD-affected patients. These mice were infected with prions derived from variant and sporadic CJD (sCJD) cases by intracerebral or intraperitoneal route, and transmission efficiency and strain phenotype were analyzed in brain and spleen. We showed that i) the main features of vCJD infection in humans, including a prominent involvement of the lymphoid tissues compared to that in sCJD infection were faithfully reproduced in such mice; ii) transmission of vCJD agent by intracerebral route could lead to the propagation of either vCJD or sCJD-like prion in the brain, whereas vCJD prion was invariably propagated in the spleen, iii) after peripheral exposure, inefficient neuroinvasion was observed, resulting in an asymptomatic infection with life-long persistence of vCJD prion in the spleen at stable and elevated levels. Conclusion/Significance. Our findings emphasize the possibility that human-to-human transmission of vCJD might produce alternative neuropathogical phenotypes and that lymphoid tissue examination of CJD cases classified as sporadic might reveal an infection by vCJD-type prions. They also provide evidence for the strong propensity of this agent to establish long-lasting, subclinical vCJD infection of lymphoreticular tissues, thus amplifying the risk for iatrogenic transmission

Amyloid-β targeting immunisation in aged non-human primate (Microcebus murinus)

International audienceNon-human primates have an important translational value given their close phylogenetic relationship to humans. Studies in these animals remain essential for evaluating efficacy and safety of new therapeutic approaches, particularly in aging primates that display Alzheimer's disease (AD) -like pathology. With the objective to improve amyloid-β (Aβ) targeting immunotherapy, we investigated the safety and efficacy of an active immunisation with an Aβ derivative, K6Aβ1-30-NH2, in old non-human primates. Thirty-two aged (4-10 year-old) mouse lemurs were enrolled in the study, and received up to four subcutaneous injections of the vaccine in alum adjuvant or adjuvant alone. Even though antibody titres to Aβ were not high, pathological examination of the mouse lemur brains showed a significant reduction in intraneuronal Aβ that was associated with reduced microgliosis, and the vaccination did not lead to microhemorrhages. Moreover, a subtle cognitive improvement was observed in the vaccinated primates, which was probably linked to Aβ clearance. This Aβ derivative vaccine appeared to be safe as a prophylactic measure based on the brain analyses and because it did not appear to have detrimental effects on the general health of these old animals. Copyright © 2023 Elsevier Inc. All rights reserved

An imprinted antisense RNA overlaps UBE3A and a second maternally expressed transcript

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