Amyloid-β pathology and cerebral amyloid angiopathy are frequent in iatrogenic Creutzfeldt-Jakob disease after dural grafting

QUESTIONS UNDER STUDY: Alzheimer-type amyloid-beta (A beta) pathology was reported in brains of individuals developing iatrogenic Creutzfeldt-Jakob disease (iCJD) after treatment with human cadaveric growth hormone, and interpreted as evidence of human transmission of A beta by the treatment. Here we investigated the prevalence of A beta pathology in other instances of iCJD related to dura mater grafts. METHODS: By use of immunohistochemistry for A beta, we investigated seven brains of patients (age range 28-63) who succumbed to iCJD after dural grafting, which had been applied by means of neurosurgery between 11 and 25 years before death. For control, we examined a series of 21 brains of age-matched (40-63 years) patients with sporadic CJD (sCJD) and an additional series of 81 sCJD cases (55-85 years) with the same methods. RESULTS: In five of seven iCJD brains, A beta was deposited in meningeal vessels as congophilic amyloid angiopathy and brain parenchymal plaques. This was significantly (p < 0.001) more frequent than in the age-matched sCJD controls and in the usual sCJD series. CONCLUSIONS: We conclude that congophilic amyloid angiopathy and brain parenchymal A beta plaques are frequent in iCJD after dural grafting. The presence of A beta pathology in young individuals is highly unusual and suggests a causal relationship to the dural grafts. Further studies will be needed to elucidate whether such pathology resulted from the seeding of A beta aggregates from the grafts to host tissues.