Evidence map›Paper›PMID 26354483›Full record

ArticleNature2015

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

Zane Jaunmuktane, Simon Mead, Matthew Ellis, Jonathan D F Wadsworth, Andrew J Nicoll, Joanna Kenny, Francesca Launchbury, Jacqueline Linehan, Angela Richard-Loendt, A Sarah Walker and 3 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 271 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
271citing papers in PubMed, 1 pooled it
30.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

271 citing papers in PubMed, 1 synthesis or guideline pooled it, 500 citations in OpenAlex.

  1. Pooled it
  2. Evidence for progressive neurodegeneration in iatrogenic cerebral amyloid angiopathy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  3. Article
  4. Strain-specific propagation of variant Creutzfeldt-Jakob disease prions in humanized neural cells.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Observational
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Beyond prion-like spreading in neurodegenerative disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  19. Article
  20. Yeast Prions: Discovery, Nature, Cellular Manipulation and Implication.Journal of microbiology and biotechnology · 2025
    Review

211 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Zane JaunmuktaneDivision of Neuropathology, The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.
Simon MeadMedical Research Council Prion Unit, Queen Square, London WC1N 3BG, UK.
Matthew EllisDepartment of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Jonathan D F WadsworthMedical Research Council Prion Unit, Queen Square, London WC1N 3BG, UK.
Andrew J NicollMedical Research Council Prion Unit, Queen Square, London WC1N 3BG, UK.
Joanna KennyMedical Research Council Prion Unit, Queen Square, London WC1N 3BG, UK.
Francesca LaunchburyDepartment of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Jacqueline LinehanMedical Research Council Prion Unit, Queen Square, London WC1N 3BG, UK.
Angela Richard-LoendtDepartment of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
A Sarah WalkerMRC Clinical Trials Unit at University College London, 125 Kingsway, London WC2B 6NH, UK.
Peter RudgeMedical Research Council Prion Unit, Queen Square, London WC1N 3BG, UK.
John CollingeMedical Research Council Prion Unit, Queen Square, London WC1N 3BG, UK.
Sebastian BrandnerDivision of Neuropathology, The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.
Medical Research Council · GBUniversity College London · GBNational Hospital for Neurology and Neurosurgery · GB

Funding

Medical Research Council MC_U123160657Medical Research Council MC_U123192748Medical Research Council MC_UU_12023/22
6 · The paper itself

Abstract

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. 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 and did not co-localize with prion protein deposition. None of these patients had pathogenic mutations, APOE ε4 or other high-risk alleles associated with early-onset Alzheimer's disease. Examination of a series of 116 patients with other prion diseases from a prospective observational cohort study 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 homogenate. 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.

Indexed as

Drug ContaminationIatrogenic DiseaseAdultAllelesAlzheimer DiseaseAmyloid beta-PeptidesAutopsyBlood VesselsCase-Control StudiesCerebral Amyloid AngiopathyCreutzfeldt-Jakob SyndromeEndothelium, VascularGray MatterHuman Growth HormoneHumansMiddle AgedAmyloid beta-PeptidesHuman Growth HormonePrions

Identifiers

PMID26354483
OpenAlexW1846679411

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.