Blood Transfusion and Brain Amyloidosis

Is misfolding of the amyloid β peptide—the primary constituent of senile plaques in Alzheimer disease and toxic cerebral vessel wall deposits in cerebral amyloid angiopathy (CAA)¹—contagious? Data from experimental and clinical sources argue that prion-like transmission of amyloid β misfolding² can indeed occur. Experimental studies as early as 1993 reported appearance of cerebral amyloid deposition following intracerebral injection of exogenous amyloid β into marmosets³ (a nonhuman primate that expresses human-like amyloid β) and subsequently in transgenic mice expressing human amyloid precursor protein.⁴ A human correlate for these findings emerged in 2015 with observation of advanced Alzheimer disease and CAA pathology in brains from individuals who had been treated with pituitary-derived human growth hormone.⁵ Subsequent clinical reports have identified early onset of the recurrent intracerebral hemorrhages (ICHs) characteristic of CAA decades after neurosurgical procedures such as dural repair with cadaveric grafts.^6,7 The reported number of suspected iatrogenic CAA cases is currently at 49 (mean age at first presentation, 43 [SD, 12] years)⁷ and is likely to grow as an echo of an era when cadaveric human tissue grafts were part of the neurosurgical toolbox. This represents a devastating illness for these individuals but nonetheless only a small share of the overall burden of CAA and Alzheimer disease.