When Peter Davies passed away on August 26, the Alzheimer’s 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 Alzheimer’s drugs and uncovered the startling complexity of the tau protein and its role in Alzheimer’s 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 was clearly one of the greatest investigators in the pantheon of Alzheimer’s 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 Alzheimer’s 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 Alzheimer’s research in the U.S.—Katzman and Terry. Terry had recruited the young hotshot from England. In 2006, Davies became the scientific director of the Litwin-Zucker Center for Research on Alzheimer’s disease at the Feinstein Institute for Medical Research, North Shore-LIJ Health System, Long Island.
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 antibodies—including MC-1 and PHF-1—trained 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 Spillantini’s tribute below). “The neuroscience community, and I especially, will be forever grateful for Peter’s generosity in sharing his wonderful library of antibodies and his boundless excitement for scientific discovery,” wrote Ralph Nixon of New York University.
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 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 Alzheimer’s Disease (ICAD), and the Potamkin Prize for Research in Pick’s, Alzheimer’s, 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 field’s 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 tau’s 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 the debates in the field, he liked my work and his comments were, for me—a young scientist at the time—very encouraging and helpful.”
Davies’s 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 Alzheimer’s 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 build my career,” wrote Lewis. “He was a great scientist and mentor, but also a kind and generous human being,” wrote Nikolaos Robakis of 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 website’s 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, Davies has been a dear, and always kind, friend of Alzforum from the get-go. Peter was a founding scientific advisor. During the site’s 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 email@example.com or type into the comment field below. —Jessica Shugart and Gabrielle Strobel
- A Tribute to Robert Katzman
- Robert D. Terry, 93, Co-Founder of U.S. Alzheimer’s Research
- Finally Introducing: A Mouse with Wildtype Human Tau That Makes Tangles
- San Francisco: Tau—Time to Shine as Therapeutic Target?
- Davies, Sperling Share 2015 Potamkin Prize
- Philadelphia: Can a Shrinking Brain Be Good for You?
- Orlando: ARF Awards 2002
- Conference Report "Cell and Molecular Biology of Alzheimer's Disease"
Research Models Citations
Image Listing with Navigation Citations
- Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet. 1976 Dec 25;2(8000):1403. PubMed.
- Wolozin BL, Pruchnicki A, Dickson DW, Davies P. A neuronal antigen in the brains of Alzheimer patients. Science. 1986 May 2;232(4750):648-50. PubMed.
- Greenberg SG, Davies P. A preparation of Alzheimer paired helical filaments that displays distinct tau proteins by polyacrylamide gel electrophoresis. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5827-31. PubMed.
- Jicha GA, Weaver C, Lane E, Vianna C, Kress Y, Rockwood J, Davies P. cAMP-dependent protein kinase phosphorylations on tau in Alzheimer's disease. J Neurosci. 1999 Sep 1;19(17):7486-94. PubMed.
- Jicha GA, O'Donnell A, Weaver C, Angeletti R, Davies P. Hierarchical phosphorylation of recombinant tau by the paired-helical filament-associated protein kinase is dependent on cyclic AMP-dependent protein kinase. J Neurochem. 1999 Jan;72(1):214-24. PubMed.
- Weaver CL, Espinoza M, Kress Y, Davies P. Conformational change as one of the earliest alterations of tau in Alzheimer's disease. Neurobiol Aging. 2000 Sep-Oct;21(5):719-27. PubMed.
- Espinoza M, de Silva R, Dickson DW, Davies P. Differential incorporation of tau isoforms in Alzheimer's disease. J Alzheimers Dis. 2008 May;14(1):1-16. PubMed.
- d'Abramo C, Acker CM, Jimenez HT, Davies P. Tau passive immunotherapy in mutant P301L mice: antibody affinity versus specificity. PLoS One. 2013;8(4):e62402. PubMed.
- Duff K, Knight H, Refolo LM, Sanders S, Yu X, Picciano M, Malester B, Hutton M, Adamson J, Goedert M, Burki K, Davies P. Characterization of pathology in transgenic mice over-expressing human genomic and cDNA tau transgenes. Neurobiol Dis. 2000 Apr;7(2):87-98. PubMed.
- Lewis J, McGowan E, Rockwood J, Melrose H, Nacharaju P, Van Slegtenhorst M, Gwinn-Hardy K, Paul Murphy M, Baker M, Yu X, Duff K, Hardy J, Corral A, Lin WL, Yen SH, Dickson DW, Davies P, Hutton M. Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat Genet. 2000 Aug;25(4):402-5. PubMed.
- Koppel J, Sousa A, Gordon ML, Giliberto L, Christen E, Davies P. Association Between Psychosis in Elderly Patients With Alzheimer Disease and Impaired Social Cognition. JAMA Psychiatry. 2018 Jun 1;75(6):652-653. PubMed.
- Gabriel SM, Haroutunian V, Powchik P, Honer WG, Davidson M, Davies P, Davis KL. Increased concentrations of presynaptic proteins in the cingulate cortex of subjects with schizophrenia. Arch Gen Psychiatry. 1997 Jun;54(6):559-66. PubMed.