Authors: Lauren Pulling
This latest instalment of our ‘Ask the Experts’ column – with Karl Frontzek (University of Zurich, Switzerland), Herbert Budka (University of Zurich, Switzerland), Marc Diamond (University of Texas Southwestern, TX, USA) and Masahito Yamada (Kanazawa University, Japan) – focuses on the question, ‘Is Alzheimer’s disease transmissible?’. In Parts 1 and 2, we explored the subject of transmissible neurological disorders and research for and against the possibility of transmissible Alzheimer’s. In this final section, our experts discuss ethical concerns, and how recent findings may affect future research and clinical practice.
Catch up on Part 1 and Part 2 of the debate here. Find out more about our experts at the bottom of this page.
Research and ethical concerns
What are the challenges in researching the transmissible qualities of Alzheimer’s disease (AD)?
MD: AD is very common, and clearly most cases are not due to exposure, as they arise spontaneously in individuals who have mostly not had exposure to growth hormone, cadaveric transplants, contaminated brain surgery instruments, etc. If exposure is through simple environmental agents, then we are all ‘exposed’ and thus the concept is relatively meaningless.
HB: There is a need for epidemiological evidence from more detailed and well-controlled epidemiological studies. As this would mostly have to rely on clinically defined disease, more detailed human tissue studies similar to Kovacs et al.  with more situations and cases studied would also be important, in particular the topical relationship between the seeding source and the seeded pathology. Kovacs et al. showed that only amyloid-beta, not tau, was propagated by dural grafts, that there was clear evidence of amyloid-beta spread from the grafting site and that the type and distribution of amyloid-betapathology differed from AD.
Last but not least, more experimental studies would be useful, in particular on potential cross-seeding, such as of tau by amyloid-beta. This might require the development of novel model designs, as presently available models that use single or double transgenics for elicitation of specific proteinopathies are unlikely to reliably reflect the multiple proteinopathies of neurodegeneration seen in the human brain.