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**flatfish** · 12-10-2015, 12:35 PM

Nature | Letter

Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

Zane Jaunmuktane,1, Simon Mead,2, 3, 4, Matthew Ellis,3, Jonathan D. F. Wadsworth,2, 3, Andrew J. Nicoll,2, 3, Joanna Kenny,2, 4, Francesca Launchbury,3, Jacqueline Linehan,2, Angela Richard-Loendt,3, A. Sarah Walker,5, Peter Rudge,2, 4, John Collinge2, 3, 4, & Sebastian Brandner1, 2, 3, Affiliations Contributions Corresponding authors Journal name: Nature Volume: 525, Pages: 247–250 Date published: (10 September 2015) DOI: doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015) Article tools PDF Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

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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 prions1, 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 angiopathy3 and did not co-localize with prion protein deposition. None of these patients had pathogenic mutations, APOE ε4 or other high-risk alleles4 associated with early-onset Alzheimer’s disease. Examination of a series of 116 patients with other prion diseases from a prospective observational cohort study5 showed minimal or no Aβ pathology in cases of similar age range, or a decade older, without APOE ε4 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 homogenate6, 7, 8, 9, 10, 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.

Subject terms: Alzheimer's disease• Prion diseases• Infection

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Terry S. Singeltary Sr. comment ;

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kind regards, terry

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Evidence for human transmission of amyloid-β pathology & cerebral amyloid angiopathy

Evidence for human transmission of amyloid-β pathology & cerebral amyloid angiopathy

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