Lectures and seminars Research Lecture at Nobel Forum with John Collinge
The theme of the lecture is "The developing understanding of prions and the implications of iatrogenic Alzheimer’s disease".
Speaker: John Collinge Professor of Neurology and Director of the MRC Prion Unit and UCL Institute of Prion Diseases.
The human transmissible spongiform encephalopathies, or prion diseases, were thought to be unique in having an aetiological triad of inherited, sporadic and acquired forms which each propagate infectious prions. Their recent ex vivo purification to homogeneity, and structural determination at near atomic resolution by cryogenic electron microscopy, confirmed that infectious prions comprise amyloid fibrillar assemblies of misfolded cellular prion protein and established the structural basis of prion strain diversity – how protein-only pathogens encode distinct phenotypes. Sustained research focus on these remarkable pathogens, spurred on by BSE crisis of 1996, has led to major and surprising insights into prion biology. While biophysically, all amyloid by definition can seed its propagation, not all amyloids can act as a pathogen - able to invade and spread in a host, evade its natural defence mechanisms and generate lethal toxicity. Experimental transmissibility of amyloid-beta and other protein assemblies seen in the commoner neurodegenerative diseases is well established in animal models but its relevance for human disease has remained controversial. The recognition of human transmission of amyloid-beta pathology from cadaver-derived pituitary growth hormone treatment and neurosurgical dura mater grafting (causing iatrogenic cerebral amyloid angiopathy) and now iatrogenic Alzheimer’s disease has changed this perspective. It appears therefore that Alzheimer’s can also have acquired in addition to sporadic and inherited aetiologies. In addition to public health considerations to minimise future iatrogenic transmission, this should now allow broader insights from prion biology to be applied to Alzheimer’s and other neurodegenerative diseases. In particular, the structural diversity, replication kinetics and interrelationships of both propagating and neurotoxic assemblies and their adaptation under host selection has important implications for understanding the phenotypic diversity of, and development of rational therapeutics for, Alzheimer’s and other diseases.
Host: Professor Janne Johansson, janne.johansson@ki.se
Contact: Pernilla Witte, Nobel Office, Nobel Forum, 08-524 861 07,
pernilla.witte@nobelprizemedicine.org