Transmission of amyloid-β protein pathology from cadaveric pituitary growth hormone

被引:134
作者
Purro, Silvia A. [1 ]
Farrow, Mark A. [1 ]
Linehan, Jacqueline [1 ]
Nazari, Tamsin [1 ]
Thomas, David X. [1 ]
Chen, Zhicheng [2 ,3 ]
Mengel, David [2 ,3 ]
Saito, Takashi [4 ]
Saido, Takaomi [4 ]
Rudge, Peter [1 ]
Brandner, Sebastian [1 ,5 ]
Walsh, Dominic M. [1 ,2 ,3 ]
Collinge, John [1 ]
机构
[1] UCL, MRC Prion Unit, Inst Prion Dis, London, England
[2] Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Lab Neurodegenerat Res, 75 Francis St, Boston, MA 02115 USA
[3] Harvard Med Sch, Boston, MA USA
[4] RIKEN, Lab Proteolyt Neurosci, Ctr Brain Sci, 2-1 Hirosawa, Wako, Saitama, Japan
[5] Natl Hosp Neurol & Neurosurg, Div Neuropathol, London, England
基金
英国医学研究理事会;
关键词
CREUTZFELDT-JAKOB-DISEASE; ALZHEIMERS-DISEASE; CEREBRAL-HEMORRHAGE; DURA-MATER; ANGIOPATHY; HYPOTHESIS; MUTATION; MODEL; SEEDS;
D O I
10.1038/s41586-018-0790-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We previously reported(1) the presence of amyloid-beta protein (A beta) deposits in individuals with Creutzfeldt-Jakob disease (CJD) who had been treated during childhood with human cadaveric pituitaryderived growth hormone (c-hGH) contaminated with prions. The marked deposition of parenchymal and vascular A beta in these relatively young individuals with treatment-induced (iatrogenic) CJD (iCJD), in contrast to other prion-disease patients and population controls, allied with the ability of Alzheimer's disease brain homogenates to seed A beta deposition in laboratory animals, led us to argue that the implicated c-hGH batches might have been contaminated with A beta seeds as well as with prions. However, this was necessarily an association, and not an experimental, study in humans and causality could not be concluded. Given the public health importance of our hypothesis, we proceeded to identify and biochemically analyse archived vials of c-hGH. Here we show that certain c-hGH batches to which patients with iCJD and A beta pathology were exposed have substantial levels of A beta(40), A beta(42) and tau proteins, and that this material can seed the formation of A beta plaques and cerebral A beta-amyloid angiopathy in intracerebrally inoculated mice expressing a mutant, humanized amyloid precursor protein. These results confirm the presence of A beta seeds in archived c-hGH vials and are consistent with the hypothesized iatrogenic human transmission of A beta pathology. This experimental confirmation has implications for both the prevention and the treatment of Alzheimer's disease, and should prompt a review of the risk of iatrogenic transmission of A beta seeds by medical and surgical procedures long recognized to pose a risk of accidental prion transmission(2,3).
引用
收藏
页码:415 / +
页数:13
相关论文
共 33 条
[1]   Amyloid-β transmission or unexamined bias? [J].
Adams, Hieab H. H. ;
Swanson, Sonja A. ;
Hofman, Albert ;
Ikram, M. Arfan .
NATURE, 2016, 537 (7620) :E7-E8
[2]   Cerebral Amyloid Angiopathy: A Systematic Review [J].
Biffi, Alessandro ;
Greenberg, Steven M. .
JOURNAL OF CLINICAL NEUROLOGY, 2011, 7 (01) :1-9
[3]   Iatrogenic Creutzfeldt-Jakob disease at the millennium [J].
Brown, P ;
Preece, M ;
Brandel, JP ;
Sato, T ;
McShane, L ;
Zerr, I ;
Fletcher, A ;
Will, RG ;
Pocchiari, M ;
Cashman, NR ;
d'Aignaux, JH ;
Cervenáková, L ;
Fradkin, J ;
Schonberger, LB ;
Collins, SJ .
NEUROLOGY, 2000, 55 (08) :1075-1081
[4]   Emerging concepts in sporadic cerebral amyloid angiopathy [J].
Charidimou, Andreas ;
Boulouis, Gregoire ;
Gurol, M. Edip ;
Ayata, Cenk ;
Bacskai, Brian J. ;
Frosch, Matthew P. ;
Viswanathan, Anand ;
Greenberg, Steven M. .
BRAIN, 2017, 140 :1829-1850
[5]   Mammalian prions and their wider relevance in neurodegenerative diseases [J].
Collinge, John .
NATURE, 2016, 539 (7628) :217-226
[6]   Collinge et al. reply [J].
Collinge, John ;
Jaunmuktane, Zane ;
Mead, Simon ;
Rudge, Peter ;
Brandner, Sebastian .
NATURE, 2016, 537 (7620) :E9-E9
[7]  
Collinge J, 2016, NATURE, V535, pE2, DOI 10.1038/nature18603
[8]   Kuru in the 21st century - an acquired human prion disease with very long incubation periods [J].
Collinge, John ;
Whitfield, Jerome ;
McKintosh, Edward ;
Beck, John ;
Mead, Simon ;
Thomas, Dafydd J. ;
Alpers, Michael P. .
LANCET, 2006, 367 (9528) :2068-2074
[9]   Risk Factors and Preventive Interventions for Alzheimer Disease State of the Science [J].
Daviglus, Martha L. ;
Plassman, Brenda L. ;
Pirzada, Amber ;
Bell, Carl C. ;
Bowen, Phyllis E. ;
Burke, James R. ;
Connolly, E. Sander, Jr. ;
Dunbar-Jacob, Jacqueline M. ;
Granieri, Evelyn C. ;
McCarty, Kathleen ;
Patel, Dinesh ;
Trevisan, Maurizio ;
Williams, John W., Jr. .
ARCHIVES OF NEUROLOGY, 2011, 68 (09) :1185-1190
[10]   Neuropathology of iatrogenic Creutzfeldt-Jakob disease and immunoassay of French cadaver-sourced growth hormone batches suggest possible transmission of tauopathy and long incubation periods for the transmission of Abeta pathology [J].
Duyckaerts, Charles ;
Sazdovitch, Veronique ;
Ando, Kunie ;
Seilhean, Danielle ;
Privat, Nicolas ;
Yilmaz, Zehra ;
Peckeu, Laurene ;
Amar, Elodie ;
Comoy, Emmanuel ;
Maceski, Aleksandra ;
Lehmann, Sylvain ;
Brion, Jean-Pierre ;
Brandel, Jean-Philippe ;
Haik, Stephane .
ACTA NEUROPATHOLOGICA, 2018, 135 (02) :201-212