Vol.:(0123456789) 1 3 Acta Neuropathologica https://doi.org/10.1007/s00401-018-1828-9 CORRESPONDENCE Fatal Aβ cerebral amyloid angiopathy 4 decades after a dural graft at the age of 2 years Dominique Hervé 1,2  · Maximilien Porché 1  · Lucie Cabrejo 3,4,5  · Céline Guidoux 3,4,5  · Elisabeth Tournier‑Lasserve 2,5,6  · Gaël Nicolas 7  · Homa Adle‑Biassette 5,8  · Isabelle Plu 9  · Hugues  Chabriat 1,2,5  · Charles Duyckaerts 9,10 Received: 29 January 2018 / Revised: 25 February 2018 / Accepted: 26 February 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018 Intracerebral injection of brain homogenates containing mis- folded Aβ can seed Aβ deposition in APP transgenic mice [7]. Parenchymal and vascular amyloid deposits have been observed in iatrogenic Creutzfeldt–Jakob disease (iCJD) caused by injection of cadaver-derived growth hormone (cGH) [1, 2, 5, 10]. This observation has raised the hypoth- esis that hormone preparations were not only contaminated with misfolded prion protein but also with Aβ aggregates able to seed amyloid formation; Aβ aggregates were, indeed, found in cGH batches produced at the time of the contamina- tion [2]. Dural grafts, up to now associated with iCJD, have also been suspected to seed Aβ accumulation mainly in the vessel walls [3, 4, 6, 9]. Seeded Aβ aggregation, however, has not been previously associated with clinical manifesta- tions [1]. We report here the case of a 46-year-old woman who died of repeated intracerebral hemorrhages caused by cerebral amyloid angiopathy (CAA), presumably related to contaminated cadaveric dura, grafted 44 years before death. In 1972, the patient, aged 2, had a severe cerebral contu- sion due to a fall from a height of 2 m. A subdural hema- toma and hemorrhagic cerebral tissue were then removed. A dural defect was flled with a graft of lyophilized human cadaveric dura mater. At the age of 46, she was hospital- ized after a sudden right sensorimotor defcit. She was not cognitively impaired and there was no clinical sign of CJD. Cerebral MRI showed two medium-sized hematomas in the left thalamus and occipital lobe, multiple lobar microbleeds, white matter hyperintensities, and a cavity left by the right frontal trauma (Fig. 1a, b). Four additional lobar hematomas occurred in a period of 6 months (three of those are shown in Fig. 1c, d). The diagnosis of CAA was made on a cerebral biopsy (with the hypothesis of angiitis). She was then preg- nant; therapeutic abortion was performed. The patient died after a last cerebral hemorrhage responsible for intracranial hypertension and brain herniation. She had no vascular risk factors. Genetic testing excluded known mutations and duplication involved in hereditary Aβ CAA (APP, PSEN1, PSEN2). The APOE genotype was ε2/ε3. The brain (1627 g) was examined after 10% formalin fxation. Three large and recent hematomas, located in the left and right frontal lobes, were observed. They had caused a central herniation and secondary hemorrhages of the brainstem. The post-traumatic cavity in the right frontal lobe was covered by scarred dura mater. Microscopically, a * Dominique Hervé dominique.herve@aphp.fr 1 Service de Neurologie, Centre de référence des maladies vasculaires rares du cerveau et de l’œil (CERVCO), APHP, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010 Paris, France 2 Inserm U1161, génétique et physiopathologie des maladies cérébro-vasculaires, Paris, France 3 Service de Neurologie et centre d’accueil et de traitement de l’attaque cérébral, APHP, Hôpital Bichat, Paris, France 4 INSERM LVTS (Laboratory for Vascular Translational Science) 1148, Paris, France 5 Université Paris 7 Diderot, Sorbonne Paris cité, Paris, France 6 Laboratoire de génétique moléculaire, APHP, Hôpital Lariboisière, Paris, France 7 Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, 76000 Rouen, France 8 Laboratoire d’anatomopathologie, APHP, Hôpital Lariboisière, Paris, France 9 Département de Neuropathologie Raymond Escourolle, GH Pitié-Salpêtrière, Faculté de médecine Sorbonne Université, Paris, France 10 Alzheimer Prions team, Institut du Cerveau et de la Moelle, Paris, France