Amyloid-β (Aβ) peptide with the capacity to seed brain amyloid deposition has been detected in archived vials of human cadaveric pituitary-derived growth hormone (c-hGH), a new paper in Nature reports. This discovery could explain why some patients who were treated with c-hGH developed Aβ pathology at a young age, despite a lack of genetic risk factors for diseases characterized by Aβ aggregation, such as Alzheimer disease (AD) and cerebral amyloid angiopathy (CAA).

Credit: Esben Klinker Hansen/Alamy Stock Photo

Between 1958 and 1985, 1,883 individuals in the UK received c-hGH to treat growth deficiency. At least 80 of the treated individuals subsequently developed Creutzfeldt–Jakob disease (CJD), which was attributed to contamination of the hormone preparation by pathogenic prion proteins. At autopsy, a number of affected individuals were additionally found to have Aβ pathology in the brain.

A team led by John Collinge at the UCL Institute of Prion Diseases, London, UK, obtained vials of c-hGH from the batches that were used in the patients who developed CJD. Biochemical analysis confirmed that these vials contained potentially pathogenic Aβ peptides.

Next, the researchers injected c-hGH from these batches into the brains of APPNL-F/NL-F knock-in mice, which express a humanized form of amyloid precursor protein and usually begin to develop Aβ pathology at ~6 months of age. Compared with control APPNL-F/NL-F mice that received phosphate buffered saline injections, the c-hGH-injected mice acquired a greater burden of Aβ deposits and CAA in the brain, implying that the hormone preparation contained Aβ seeding activity.

the c-hGH-injected mice acquired a greater burden of Aβ deposits and CAA in the brain

Collinge and colleagues emphasize that these findings do not suggest that AD is contagious. Nevertheless, as they write in the paper, “it will be important to consider introducing improved methods for removing proteopathic seeds from surgical instruments on a precautionary basis.”