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More than two hundred individuals developed Creutzfeldt-Jakob disease (CJD) worldwide as a result of treatment, typically in childhood, with human cadaveric pituitary-derived growth hormone contaminated with prions (1, 2). Although such treatment ceased in 1985, iatrogenic CJD (iCJD) continues to emerge because of the prolonged incubation periods seen in human prion infections. Unexpectedly, in an autopsy study of eight individuals with iCJD, aged 36-51 years, in four we found moderate to severe grey matter and vascular amyloid-β (Aβ) pathology. The Aβ deposition in the grey matter was typical of that seen in Alzheimer's disease and Aβ in the blood vessel walls was characteristic of cerebral amyloid angiopathy (3) and did not co-localize with prion protein deposition. None of these patients had pathogenic mutations, APOE ζ4 or other high-risk alleles (4) associated with early-onset Alzheimer's disease. Examination of a series of 116 patients with other prion diseases from a prospective observational cohort study (5) showed minimal or no Aβ pathology in cases of similar age range, or a decade older, without APOE ζ4 risk alleles. We also analysed pituitary glands from individuals with Aβ pathology and found marked Aβ deposition in multiple cases. Experimental seeding of Aβ pathology has been previously demonstrated in primates and transgenic mice by central nervous system or peripheral inoculation with Alzheimer's disease brain homogenate (6-11). The marked deposition of parenchymal and vascular Aβ in these relatively young patients with iCJD, in contrast with other prion disease patients and population controls, is consistent with iatrogenic transmission of Aβ pathology in addition to CJD and suggests that healthy exposed individuals may also be at risk of iatrogenic Alzheimer's disease and cerebral amyloid angiopathy. These findings should also prompt investigation of whether other known iatrogenic routes of prion transmission may also be relevant to Aβ and other proteopathic seeds associated with neurodegenerative and other human diseases., Human transmission of prion disease has occurred as a result of a range of medical and surgical procedures worldwide as well as by endocannibalism in Papua New Guinea, with incubation [...]

To identify biomarkers for glioma growth, invasion and progression, we used a candidate gene approach in mouse models with two complementary brain tumour phenotypes, developing either slow-growing, diffusely infiltrating gliomas or highly proliferative, non-invasive primitive neural tumours. In a microRNA screen we first identified microRNA-449a as most significantly differentially expressed between these two tumour types. miR-449a has a target dependent effect, inhibiting cell growth and migration by downregulation of CCND1 and suppressing neural phenotypes by inhibition of G protein coupled-receptor (GPR) 158. GPR158 promotes glioma stem cell differentiation and induces apoptosis and is highest expressed in the cerebral cortex and in oligodendrogliomas, lower in IDH mutant astrocytomas and lowest in the most malignant form of glioma, IDH wild-type glioblastoma. The correlation of GPR158 expression with molecular subtypes, patient survival and therapy response suggests a possible role of GPR158 as prognostic biomarker in human gliomas.