Iatrogenic Alzheimer's disease in recipients of cadaveric pituitary-derived growth hormone.


Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
Feb 2024
Historique:
received: 03 10 2023
accepted: 17 11 2023
medline: 22 2 2024
pubmed: 30 1 2024
entrez: 29 1 2024
Statut: ppublish

Résumé

Alzheimer's disease (AD) is characterized pathologically by amyloid-beta (Aβ) deposition in brain parenchyma and blood vessels (as cerebral amyloid angiopathy (CAA)) and by neurofibrillary tangles of hyperphosphorylated tau. Compelling genetic and biomarker evidence supports Aβ as the root cause of AD. We previously reported human transmission of Aβ pathology and CAA in relatively young adults who had died of iatrogenic Creutzfeldt-Jakob disease (iCJD) after childhood treatment with cadaver-derived pituitary growth hormone (c-hGH) contaminated with both CJD prions and Aβ seeds. This raised the possibility that c-hGH recipients who did not die from iCJD may eventually develop AD. Here we describe recipients who developed dementia and biomarker changes within the phenotypic spectrum of AD, suggesting that AD, like CJD, has environmentally acquired (iatrogenic) forms as well as late-onset sporadic and early-onset inherited forms. Although iatrogenic AD may be rare, and there is no suggestion that Aβ can be transmitted between individuals in activities of daily life, its recognition emphasizes the need to review measures to prevent accidental transmissions via other medical and surgical procedures. As propagating Aβ assemblies may exhibit structural diversity akin to conventional prions, it is possible that therapeutic strategies targeting disease-related assemblies may lead to selection of minor components and development of resistance.

Identifiants

pubmed: 38287166
doi: 10.1038/s41591-023-02729-2
pii: 10.1038/s41591-023-02729-2
pmc: PMC10878974
doi:

Substances chimiques

Growth Hormone 9002-72-6
Amyloid beta-Peptides 0
Prions 0
Biomarkers 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

394-402

Subventions

Organisme : Medical Research Council
ID : MC_UU_00024/9
Pays : United Kingdom

Informations de copyright

© 2024. The Author(s).

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Auteurs

Gargi Banerjee (G)

MRC Prion Unit at UCL and UCL Institute of Prion Diseases, London, UK.
National Prion Clinic, National Hospital for Neurology and Neurosurgery, London, UK.

Simon F Farmer (SF)

Department of Neurology, National Hospital for Neurology and Neurosurgery, London, UK.

Harpreet Hyare (H)

UCL Queen Square Institute of Neurology, London, UK.
Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, UK.

Zane Jaunmuktane (Z)

Department of Clinical and Movement Neurosciences and Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London, UK.
Division of Neuropathology, National Hospital for Neurology and Neurosurgery, London, UK.

Simon Mead (S)

MRC Prion Unit at UCL and UCL Institute of Prion Diseases, London, UK.
National Prion Clinic, National Hospital for Neurology and Neurosurgery, London, UK.

Natalie S Ryan (NS)

Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
UK Dementia Research Institute at UCL, London, UK.

Jonathan M Schott (JM)

Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
UK Dementia Research Institute at UCL, London, UK.

David J Werring (DJ)

Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK.
Stroke Service, National Hospital for Neurology and Neurosurgery, London, UK.

Peter Rudge (P)

MRC Prion Unit at UCL and UCL Institute of Prion Diseases, London, UK.
National Prion Clinic, National Hospital for Neurology and Neurosurgery, London, UK.

John Collinge (J)

MRC Prion Unit at UCL and UCL Institute of Prion Diseases, London, UK. jc@prion.ucl.ac.uk.
National Prion Clinic, National Hospital for Neurology and Neurosurgery, London, UK. jc@prion.ucl.ac.uk.

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