The idea that infectious agents in the brain have a role in the pathogenesis of Alzheimer disease (AD) was proposed nearly 30 years ago. However, this theory failed to gain substantial traction and was largely disregarded by the AD research community for many years. Several recent discoveries have reignited interest in the infectious theory of AD, culminating in a debate on the topic at the Alzheimer’s Association International Conference (AAIC) in July 2019. In this Viewpoint article, experts who participated in the AAIC debate weigh up the evidence for and against the infectious theory of AD and suggest avenues for future research and drug development.
Ruth F. Itzhaki has a BSc in physics and an MSc and a PhD in biophysics from the University of London, UK. She worked as a postdoctoral researcher at the University of Cambridge, UK, where she held a Beit Memorial Fellowship in the Radiotherapeutics Department and the Wheldale Onslow Fellowship at Newnham College. She then moved to the Paterson Laboratories, Manchester, UK, and later to Manchester University. Her research topics have been diverse, and she is currently studying viruses in Alzheimer disease (AD) and the role of apolipoprotein E in infection. She is now an Emeritus Professor at Manchester University and a Visiting Professor at Oxford University, UK.
Todd E. Golde is a Professor of Neuroscience and Director of the Evelyn F. and William L. McKnight Brain Institute at the University of Florida, Gainesville, FL, USA. He also directs the NIH-funded Florida Alzheimer’s Disease Research Center. With over 30 years of research experience in AD, Dr Golde has made substantial contributions to the field. His early studies helped establish the underpinnings of the amyloid hypothesis and provided insight into the therapeutic targeting of amyloid deposition. More recently, he has focused on the role of the immune system and stress pathways in AD.
Michael T. Heneka studied medicine in Tübingen (Germany), Lausanne (Switzerland) and London (UK) and thereafter specialized in clinical neurology and neurosciences. He is currently serving as the Director of the Department of Neurodegenerative Disease and Geriatric Psychiatry at the University of Bonn Medical Center, Bonn, Germany. His research focuses on the interaction between immunological and neurodegenerative processes.
Ben Readhead is an Australian-born medical practitioner. He is passionate about innovation in the life sciences, with a focus on the application of biomedical informatics to enable precision medicine and improve patient care. His research is focused on developing and applying integrative genomics approaches to high-dimensional biomedical data with the goal of improving therapeutic options for patients with neurodegenerative diseases, particularly AD. He is especially interested in understanding the complex web of interactions between the brain microbiome and host biology in the context of neurodegenerative disease.
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T.E.G. is a co-founder and is on the scientific advisory board (SAB) of Lacerta Therapeutics. He is an SAB member for Promis Therapeutics and has served on SABs for Abbvie, Pfizer, Novartis, Roche/Genetic, Bristol Myers Squibb, Eli Lilly and Biogen. He is an inventor on a number of patents relating to Alzheimer disease therapeutics. He receives funding from the NIH, the Facial Pain Research Foundation and the State of Florida. M.T.H. serves as an advisory board member for IFM Therapeutics, Alector and Tiaki. The other authors declare no competing interests.
Dr Robert Moir (1961–2019) was the fifth participant of the AAIC debate, but sadly passed away as this manuscript was being prepared. The authors dedicate this Viewpoint to him as a tribute to an indomitable and original thinker, brilliant and unorthodox scientist, and true forerunner of research into the role of microorganisms in Alzheimer disease.
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Itzhaki, R.F., Golde, T.E., Heneka, M.T. et al. Do infections have a role in the pathogenesis of Alzheimer disease?. Nat Rev Neurol 16, 193–197 (2020). https://doi.org/10.1038/s41582-020-0323-9