In the last 6 years, following the first pathological description of presumed amyloid-beta (Aβ) transmission in humans (in 2015) and subsequent experimental confirmation (in 2018), clinical cases of iatrogenic cerebral amyloid angiopathy (CAA)—attributed to the transmission of Aβ seeds—have been increasingly recognised and reported. This newly described form of CAA is associated with early disease onset (typically in the third to fifth decade), and often presents with intracerebral haemorrhage, but also seizures and cognitive impairment. Although assumed to be rare, it is important that clinicians remain vigilant for potential cases, particularly as the optimal management, prognosis, true incidence and public health implications remain unknown. This review summarises our current understanding of the clinical spectrum of iatrogenic CAA and provides a diagnostic framework for clinicians. We provide clinical details for three patients with pathological evidence of iatrogenic CAA and present a summary of the published cases to date (n=20), identified following a systematic review. Our aims are: (1) To describe the clinical features of iatrogenic CAA, highlighting important similarities and differences between iatrogenic and sporadic CAA; and (2) To discuss potential approaches for investigation and diagnosis, including suggested diagnostic criteria for iatrogenic CAA.
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Contributors GB designed and conceptualised study, collected the clinical data, performed the literature searches, and drafted the manuscript. KS collected the clinical data and revised the manuscript for intellectual content. MEA prepared figure 2, and revised the manuscript for intellectual content. ZJ and SB contributed to the neuropathological data, and revised the manuscript for intellectual content. APJ, JG, AKT, SFF, RS, PR and JMS all contributed to the clinical care of the patients described, and revised the manuscript for intellectual content. HH, SM and JC contributed the genetic analyses, and revised the manuscript for intellectual content. DJW contributed to the clinical care of the patients and the design and conceptualisation of the study, and revised the manuscript for intellectual content.
Funding GB holds a clinical lectureship funded by Alzheimer’s Research UK (ARUK-CRF2020A-003), the Stroke Association (SA L-MP 20\100002) and the NIHR (no award/grant number). ZJ, AKT, SFF and SB are supported by the UK Department of Health’s NIHR Biomedical Research Centre’s funding scheme to UCLH (no award/grant number). SM and JC are NIHR senior investigators (NF-SI-0617-10175 and NF-SI-0611-10073, respectively). The MRC Prion Unit at UCL is core funded by the UK Medical Research Council (no award/grant number).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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