Infectious prions do not induce Aβ deposition in an in vivo seeding model
An increasing number of studies have suggested that certain cases of iatrogenic Creutzfeldt–Jakob disease (iCJD) that harbor significant β-amyloid (Aβ) pathology are the result of aggregated Aβ transmission to patients during the same procedure that caused prion disease [2, 4, 7, 8, 11, 13, 17]. The source of iatrogenic contamination has been observed both for human growth hormone infusions and dura mater grafts, arguing against a treatment specific effect. Intriguingly, recent work has also observed suspected Aβ pathology transmission in post-mortem samples that received growth hormone treatments but did not develop CJD . Yet another study suggested that neurosurgery with Aβ-contaminated tools can transmit Aβ pathology and lead to intracerebral hemorrhage . These findings have been debated in the context of whether Aβ pathology is truly transmissible and whether Alzheimer’s disease could subsequently develop.
It is well known that aggregated Aβ can nucleate the misfolding and...
This study was partly supported by the EC Joint Programme on Neurodegenerative Diseases (REfrAME and NeuTarget), CJD Foundation Inc. and German Ministry of Education and Research Programme (UndoAD). We also thank K. Hartmann and U. Obermüller for technical assistance.
- 2.Cali I, Cohen ML, Hasmall Yi US, Parchi P, Giaccone G, Collins SJ, Kofskey D, Wang H, McLean CA, Brandel JP et al (2018) Iatrogenic Creutzfeldt-Jakob disease with Amyloid-beta pathology: an international study. Acta Neuropathol Commun 6:5. https://doi.org/10.1186/s40478-017-0503-z CrossRefPubMedPubMedCentralGoogle Scholar
- 3.Dohler F, Sepulveda-Falla D, Krasemann S, Altmeppen H, Schluter H, Hildebrand D, Zerr I, Matschke J, Glatzel M (2014) High molecular mass assemblies of amyloid-beta oligomers bind prion protein in patients with Alzheimer’s disease. Brain 137:873–886. https://doi.org/10.1093/brain/awt375 CrossRefPubMedGoogle Scholar
- 4.Duyckaerts C, Sazdovitch V, Ando K, Seilhean D, Privat N, Yilmaz Z, Peckeu L, Amar E, Comoy E, Maceski A et al (2018) 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. Acta Neuropathol 135:201–212. https://doi.org/10.1007/s00401-017-1791-x CrossRefPubMedGoogle Scholar
- 5.Eisele YS, Obermuller U, Heilbronner G, Baumann F, Kaeser SA, Wolburg H, Walker LC, Staufenbiel M, Heikenwalder M, Jucker M (2010) Peripherally applied Abeta-containing inoculates induce cerebral beta-amyloidosis. Science 330:980–982. https://doi.org/10.1126/science.1194516 CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Hamaguchi T, Taniguchi Y, Sakai K, Kitamoto T, Takao M, Murayama S, Iwasaki Y, Yoshida M, Shimizu H, Kakita A et al (2016) Significant association of cadaveric dura mater grafting with subpial Abeta deposition and meningeal amyloid angiopathy. Acta Neuropathol 132:313–315. https://doi.org/10.1007/s00401-016-1588-3 CrossRefPubMedGoogle Scholar
- 10.Herve D, Porche M, Cabrejo L, Guidoux C, Tournier-Lasserve E, Nicolas G, Adle-Biassette H, Plu I, Chabriat H, Duyckaerts C (2018) Fatal Abeta cerebral amyloid angiopathy 4 decades after a dural graft at the age of 2 years. Acta Neuropathol. https://doi.org/10.1007/s00401-018-1828-9 PubMedGoogle Scholar
- 11.Jaunmuktane Z, Mead S, Ellis M, Wadsworth JD, Nicoll AJ, Kenny J, Launchbury F, Linehan J, Richard-Loendt A, Walker AS et al (2015) Evidence for human transmission of amyloid-beta pathology and cerebral amyloid angiopathy. Nature 525:247–250. https://doi.org/10.1038/nature15369 CrossRefPubMedGoogle Scholar
- 15.Meyer-Luehmann M, Coomaraswamy J, Bolmont T, Kaeser S, Schaefer C, Kilger E, Neuenschwander A, Abramowski D, Frey P, Jaton AL et al (2006) Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host. Science 313:1781–1784. https://doi.org/10.1126/science.1131864 CrossRefPubMedGoogle Scholar
- 16.Morales R, Estrada LD, Diaz-Espinoza R, Morales-Scheihing D, Jara MC, Castilla J, Soto C (2010) Molecular cross talk between misfolded proteins in animal models of Alzheimer’s and prion diseases. J Neurosci 30:4528–4535. https://doi.org/10.1523/JNEUROSCI.5924-09.2010 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Ritchie DL, Adlard P, Peden AH, Lowrie S, Le Grice M, Burns K, Jackson RJ, Yull H, Keogh MJ, Wei W et al (2017) Amyloid-beta accumulation in the CNS in human growth hormone recipients in the UK. Acta Neuropathol 134:221–240. https://doi.org/10.1007/s00401-017-1703-0 CrossRefPubMedPubMedCentralGoogle Scholar