Amyloid-β pathology induced in humans

Abstract

People who died of the neurodegenerative condition Creutzfeldt-Jakob disease after treatment with cadaver-derived human growth hormone also developed some of the pathological traits of Alzheimer's disease. See Letter p.247 Treatment of children with human cadaver-derived growth hormone (hGH) contaminated with prions resulted in iatrogenic transmission of Creutzfeldt–Jakob disease (iCJD). While such treatment ceased in 1985, CJD has a long incubation time and new cases are still emerging. Unexpectedly, an autopsy study of eight such iCJD patients, aged 36–51 years old, has revealed amyloid-β deposition in the grey matter typical of that seen in Alzheimer's disease and Aβ in the blood vessel walls characteristic of cerebral amyloid angiopathy. None of these patients had pathogenic mutations or high-risk alleles associated with early onset Alzheimer's disease. Importantly, Aβ pathology was detected only in prion-infected individuals who received hGH. This is consistent with iatrogenic transmission of Aβ pathology in addition to CJD, and suggests that healthy hGH exposed individuals may also be at risk of iatrogenic Alzheimer's disease and cerebral amyloid angiopathy.