04 Sep 2020

When Peter Davies passed away on August 26, the Alzheimers research community lost a brilliant mind, and a truly generous human being. Davies died at age 72, after a long battle with cancer.

His discoveries paved the way for the first Alzheimers drugs and uncovered the startling complexity of the tau protein and its role in Alzheimers and other tauopathies. In their tributes on Alzforum, fellow scientists particularly recalled Davies generous sharing of antibody reagents and spirited conversations with him about the pathophysiology of AD, as much as they saluted his scientific achievements.

Peter Davies

Peter was clearly one of the greatest investigators in the pantheon of Alzheimers researchers. I knew him as a dear friend and valued mentor since the 80s. I always valued his great balance of scientific objectivity and empathy, especially for young investigators, Rudy Tanzi of Massachusetts General Hospital wrote to Alzforum.

Davies grew up in Wales, and studied biochemistry at the University of Leeds in northern England. After completing postdoctoral work at the University of Edinburgh, he joined the staff of the Medical Research Council Brain Metabolism Unit there in 1974. It was in Edinburgh that Davies began to explore Alzheimers disease.

Published on Christmas Day in 1976, his first AD paper turned out to be a gift to the field. He reported that the cholinergic system took a severe hit in the disease, a discovery that led to the development of acetylcholinesterase inhibitors, the first FDA-approved treatments for the disease (Davies and Maloney, 1976; Alzforum timeline).

His move, in 1977, to Albert Einstein College of Medicine in the Bronx, New York, brought him under the tutelage of the two great (and late) Bobs of early Alzheimers research in the U.S.Katzmanand Terry. Terry had recruited the young hotshot from England. In 2006, Davies became the scientific director of the Litwin-Zucker Center for Research on Alzheimers disease at theFeinstein Institute for Medical Research,North Shore-LIJ Health System, Long Island.

Peter Davies, Robert D. Terry, and Robert Katzman. Image credit: Peter Davies

Davies is perhaps best known for his work on the myriad forms of tau. He helped lay bare the devilish complexity of this microtubule-binding, tangle-forming protein. Starting with the development of Alz50, the first antibody to latch onto misfolded tau, Davies group went on to develop many more such antibodiesincluding MC-1and PHF-1trained against different forms the protein (Wolozin et al., 1986; Greenberg and Davies, 1990;Jicha et al., 1999).

Davies readily shared these reagents with other researchers. If you ever wanted to obtain and utilize any of the very useful antibodies that his laboratory created and you sent him an email, a few days later the antibody would just appear in your lab, recalled David Holtzman of Washington University in St. Louis. Throughout the field, Davies antibodies proved essential to pivotal discoveries about tau pathobiology (for detail, see Michel Goedert and Maria Grazia Spillantinis tribute below). The neuroscience community, and I especially, will be forever grateful for Peters generosity in sharing his wonderful library of antibodies and his boundless excitement for scientific discovery, wrote Ralph Nixon of New York University.

Over more than three decades, Davies published some 250 papers on tau, from its phosphorylation to truncation (Jicha et al., 1999;Weaver et al., 2000; Espinoza et al., 2008; dAbramo et al., 2013).

He kept an eye toward targeting toxic forms of the protein with therapeutics, and Zagotenemab,a derivative of his MC-1 antibody developed by Lilly, is currently finishing a Phase 2 trial in 285 people with early AD.

Davies also generated mouse models, including the hTau mice expressing all six isoforms of human tau (Duff et al., 2000; Nov 2001 news;May 2011 conference news).

Davies received numerous awards for his scientific achievements, including two MERIT awards from the National Institutes of Health, a Lifetime Achievement Award from the International Congress on Alzheimers Disease (ICAD), and the Potamkin Prize for Research in Picks, Alzheimers, and Related Diseases (Apr 2015 news).

For some years, Davies emphasis on the role of tau pathology in AD put him at odds with those who centered their research on amyloid. He was a witty voice for the tauist side during the fields sometimes truculent, and long past, period of division into baptist-versus-tauist camps. But for all Davies zest for tau, he pursued a broad understanding of the disease.

Publicly, Peter kept faith as a tauist and championed taus role in AD and related disorders, recalled Todd Golde of the University of Florida in Gainesville. In a more private setting though, Peter always had a quite encompassing view of the complexities of AD.

For him, tau was worthy of defense, but it was not a religion, noted Nixon. His ecumenicism as a scientist allowed him to embrace varied viewpoints on AD pathogenesis and to convey this broader understanding to junior scientists.

Davies was a skilled debater. He energetically questioned entrenched assumptions in the field (e.g., Mar 2006 webinar;Jul 2004 conference news).We had many friendly and interesting discussions about presenilin, wrote Bart De Strooper of KU Leuven in Belgium.Despite me being in the amyloid wing of thedebates in the field, he liked my work and his comments were, for mea young scientist at the timevery encouraging and helpful.

Daviess deep understanding of the disease made him a sought-after advisor, noted Benjamin Wolozin of Boston University. Indeed, chatting with Peter into the evening was always an immense pleasure because he always offered a challenging view of the pathophysiology of Alzheimers disease.

Throughout his career, Davies mentored budding researchers, many of whom are still working in the field. Peter was one of the first people Mike Hutton and I talked to about our JNPL3 tau model,and he did some of the first characterization of the mice, Jada Lewis of the University of Florida, Gainesville, wrote to Alzforum (Lewis et al. 2000). Peter believed in our model well before I did. At the time, I was brand-new to the field and had no clue what an honor it was to have Peter involved.I credit this initial collaboration and his subsequent generosity with his resources in helping buildmy career, wrote Lewis. He was a great scientist and mentor, but also a kind and generous human being, wrote Nikolaos Robakisof Mount Sinai Medical Center in New York.

Perhaps less well known to this audience is that Davies was actively interested in human suffering from schizophrenia. He published around 10 studies on psychosis, in tau transgenic mice, in human cohorts, and at the level of human synaptic neuropathology (Koppel et al,., 2018; Gabriel et al., 1997).

Davies received the inaugural Alzforum Mensch Award in 2002, a more light-hearted time during this websites early years, when Alzheimerologists used to get together during the Society for Neuroscience meeting for a sometimes raucous hour of comedy, karaoke, and dance shared over beers (Nov 2002 conference news).

More seriously, Davieshas been a dear, and always kind, friend of Alzforum from the get-go. Peter was a founding scientific advisor. During the sites early years, Peter penned conference dispatches for Alzforum (e.g., Sept 2002 conference news). Subsequently, he contributed 25 written commentaries plus countless in-person tips on where the field was headed. He left too soon, and will be missed.

Do you have special memories of Peter? How did he influence your work and career? Found a fun photo? To add to our collective tribute, email gstrobel@alzforum.org or type into the comment field below. Jessica Shugart and Gabrielle Strobel

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Peter Davies, Beloved Giant of Alzheimer's Disease Research, 72 - Alzforum