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John Q. Trojanowski, ‘tour de force’ in neurodegeneration (1946–2022)

John Q. Trojanowski, distinguished neuropathologist and scientist, died on February 8, 2022, at the age of 75. At 6 ft 4 in., with a ready laugh and a talent for asking the right question, John was a towering figure in neurodegenerative disease research. Alongside his life partner, Virginia M.-Y. Lee, John shaped our understanding of the proteins that lie at the heart of Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease, and amyotrophic lateral sclerosis.

Credit: Office of University Communications, University of Pennsylvania

John was literally born on the move, while his Air Force family was relocating from Florida to Maine in 1946. He stayed on the move for the next thirty years, studying in Vienna while majoring in German literature at a small college in Wilkes-Barre, Pennsylvania; doing research at Erasmus University in Rotterdam while earning his MD and PhD degrees at Tufts University. He trained in clinical neuropathology at the Massachusetts General Hospital in Boston, where he finally found his center of gravity in a pianist-turned-biochemist named Virginia Lee. The two married in 1979 and arrived at the University of Pennsylvania in 1980, where they would forge an extraordinary, decades-spanning scientific partnership.

Although he would stay put geographically from that point onwards, eventually becoming the Director of the Institute on Aging and the William Maul Measey-Truman G. Schnabel, Jr., MD Professor of Geriatrics and Gerontology at the Perelman School of Medicine at the University of Pennsylvania, John never stopped moving in any other sense. He was early to realize that neurodegenerative disease would become a major problem, and major research focus, of our time. He entered the field of Alzheimer’s research against the advice of more senior colleagues, who told him it was “a morass.” John and Virginia proved that this was most definitely not the case, by creating guideposts in this terra nova with a foundational discovery every decade. The 1990s were marked by their discovery that the neurofibrillary tangles found in the brains of individuals with Alzheimer’s disease were composed of an abnormally phosphorylated form of the protein tau1; the 2000s by their discovery that a poorly characterized protein named TDP-43 comprised the signature inclusions of frontotemporal dementia and amyotrophic lateral sclerosis2; and the 2010s by their work demonstrating that the cell-to-cell transmission of α-synuclein might lie at the heart of disease progression in Parkinson’s disease3. Many awards followed, among them the Potamkin Prize for Research in Pick’s, Alzheimer’s, and Related Disease (1996) and the Alzheimer’s Association Lifetime Achievement Award (2018).

Not content with his role in this fundamental scientific work, John also pushed for the translation of discoveries into useful biomarkers4 and eventual therapies for patients. He understood innately the importance of disease advocacy and scientific communication, and he threw himself into these activities with his trademark energy and passion. He made educational films for the lay public. He advocated before lawmakers. He was a visible, beloved fixture at research meetings, first up at the microphone after talks, with a probing, if sometimes loquacious, query.

Those of us who were lucky enough to count John Trojanowski as a colleague remember his generosity and his knack for bringing out the best in others. He created a culture of collaboration at every scale. Within the international research community, John was a driving force for the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a public–private partnership focused on the early detection and tracking of Alzheimer’s disease, for which he served as Biomarker Core Leader from its founding in 2004 until his death in 2022. Within the Penn community, he created a shared resource of samples and data from patients with neurodegenerative diseases that now includes more than 6,000 unique individuals — a process that required him to cajole generations of clinicians and researchers to cooperate for a common cause. With ADNI and with the Penn patient samples, John championed an ‘open access’ model before the idea was in vogue, amplifying the impact of this work.

Within the Center for Neurodegenerative Disease Research (CNDR) that he co-directed with Virginia Lee, John Trojanowski fostered trainees who would go on to lead efforts in academic institutions around the globe, as well as in industry, while feeling a connection with each other. Having trained as a postdoc myself at the CNDR, as both a new mother and scientific late bloomer, I will also note that John was an extraordinary enabler of women scientists. His at-times ‘spirited’ disagreements with Virginia were legendary5, but they were the sparring matches one might have with one’s most admired colleague. He considered women to be formidable and worthy of respect, and he never patronized. So many of us could count on feeling absolutely at home in his company.

In the lab, in the public eye, in his personal life, John did things with flair. His slightly-glam-rock hair of the 80s and 90s evolved into a distinct uniform of stylish glasses and mandarin-collared dress shirts. He squeezed oranges for juice, and he ground his own coffee. He quoted Goethe. He sported the fanny pack of many a lifelong biker, which he was, riding to and from work well into his 60s.

When news of John’s untimely death spread, a member of my own lab recalled that John would often call our co-authored papers an “amazing tour de force.” We laughed at the obvious exaggeration. But in retrospect, I think John meant it every time, to his many trainees and colleagues, across what must be hundreds of examples. We, in turn, felt buoyed by his confidence, since John’s own life was, of course, the true tour de force, for which we would suggest no emendations.

References

  1. Lee, V. M.-Y., Balin, B. J., Otvos, L. Jr & Trojanowski, J. Q. A68: a major subunit of paired helical filaments and derivatized forms of normal Tau. Science 251, 675–678 (1991).

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  2. Neumann, M. et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130–133 (2006).

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  3. Luk, K. C. et al. Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338, 949–953 (2012).

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  4. Shaw, L. M. et al. Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann. Neurol. 65, 403–413 (2009).

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Correspondence to Alice S. Chen-Plotkin.

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Chen-Plotkin, A.S. John Q. Trojanowski, ‘tour de force’ in neurodegeneration (1946–2022). Nat Neurosci 25, 675–676 (2022). https://doi.org/10.1038/s41593-022-01087-5

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