LAUSR

Creutzfeldt–Jakob disease (CJD) is a progressive neurodegenerative condition caused by the accumulation of toxic forms of prion protein in the brain. In 1985, reports emerged of patients who had developed CJD following treatment with cadaveric human growth hormone contaminated with prion protein, suggesting a transmissible aetiology. More recently detailed pathological analyses of brain tissue in these patients have unexpectedly revealed the co-existence of amyloid-beta protein (Aβ), the most common misfolded protein seen in the ageing brain, which is also implicated in the aetiology of Alzheimer’s disease and cerebral amyloid angiopathy. Both prion protein and Aβ protein share similar properties including the ability to survive normal sterilisation procedures. They are both able to grow and spread via nucleation-dependent polymerisation processes, in which oligomeric seeds can promote the formation of an ordered nucleus that can form larger fibrils. The long incubation periods of these proteins can result in clinical and pathological evidence of disease becoming apparent decades after inoculation. In this month’s journal club, we review three recent studies that explore the potential transmissibility of Aβ pathology and which may have far-reaching implications. Two papers examine the pathological phenotype of protein accumulation in patients who died from iatrogenic CJD following growth hormone supplementation. Both suggest that the high proportion of Aβ pathology seen in this group may indicate that the Aβ protein is transmissible via contaminated human growth hormone. The authors in these papers also suggest that contamination may occur via other sources such as human dura mater grafting and neurosurgical instrumentation. The third and most recent paper attempts to shed light on the aetiology of young-onset cerebral amyloid angiopathy in patients who had undergone childhood neurosurgery.