Dr. John Q. Trojanowski, a neuropathologist whose work was at the forefront of research on Alzheimer’s and other neurodegenerative diseases, died on Feb. 8 in a hospital in Philadelphia. He was 75.
His wife and longtime collaborator, Virginia M.-Y. Lee, said the cause was complications of chronic spinal cord injuries.
Dr. Trojanowski “was a giant in the field,” said Leslie Shaw, a professor with Dr. Trojanowski in the department of pathology and laboratory medicine at the University of Pennsylvania — adding that he meant that in two ways.
At 6 feet 4 inches, Dr. Trojanowski towered over his colleagues. And, Dr. Shaw said, he was also a towering figure in his field, whose scientific contributions were “phenomenal” because they combined pathology and biochemistry to figure out what goes wrong, and why, when people get diseases as disparate as Alzheimer’s, Parkinson’s and A.L.S. The results can lead to improved diagnosis and potential treatments.
Key to the work Dr. Trojanowski did with Dr. Lee was their establishment of a brain bank: stored brains from patients with diseases like Alzheimer’s and Parkinson’s, as well as from people without degenerative brain diseases. It allowed them to compare the brains of people with and without the conditions and ask what proteins were involved in the diseases and what brain regions were affected.
Among their first quests was an attempt to solve the mystery of strange areas in the brains of people with Alzheimer’s. Known as tangles and first described by Alois Alzheimer himself at the turn of the 20th century, they look like twisted strands of spaghetti in dying nerve cells. In 1991, Dr. Trojanowski and Dr. Lee determined that the regions are made up of a malformed protein called tau, which causes the structure of nerve cells to collapse.
At a time when most Alzheimer’s researchers and drug companies were focused on a different protein, amyloid, Dr. Trojanowski and Dr. Lee insisted that tau was equally important. They then discovered that it also played a central role in a rare group of degenerative dementias known as frontotemporal lobar degeneration.
The team went on to discover that another abnormal protein, alpha-synuclein, accumulates in areas known as Lewy bodies in the brains of people with Parkinson’s disease.
Among their most striking discoveries was that the abnormal folding of a protein known as TDP-43 can cause what is now recognized as a common type of dementia, which is associated with profound amnesia and is often present along with Alzheimer’s disease.
Dr. Trojanowski and Dr. Lee published dozens of influential papers and were among the top 10 most highly cited neuroscientists from 1997 to 2007.
In an online posting of tributes by former students and colleagues, Dr. Jeffrey Kordower of Rush University Medical Center in Chicago said that Dr. Trojanowski was “the scientific light that the rest of us followed.”
John Quinn Trojanowski was born in Bridgeport, Conn., on Dec. 17, 1946, the second of Margaret (Quinn) Trojanowski and Maurice Trojanowski’s seven children. Because his father was an officer in the Air Force, he spent his childhood and adolescence moving every few years among Air Force bases in the United States and Germany.
After attending a long list of schools, he graduated from Notre Dame High School in Fairfield, Conn., in 1965. He majored in German studies at King’s College in Wilkes-Barre, Pa., and graduated in 1970. In 1976, he received a combined M.D.-Ph.D. degree from Tufts University.
Dr. Trojanowski met Dr. Lee when she was doing postdoctoral training at Boston Children’s Hospital and he was studying at Harvard Medical School, with which the hospital is affiliated. They married in 1979 and both became faculty members at the University of Pennsylvania, where they worked as a research team.
“It was really exciting working with John,” Dr. Lee said. “We literally spent 24/7 together.”
Science was always on their minds, she said, a constant source of conversation, and Dr. Trojanowski had few activities outside of his work.
And, she added, he never really had close friends, other than her. In part, she said, that was because he moved so often when he was growing up. But it was also because the two of them were so close.
“We were very happy together,” she said. “He was pretty content just to spend his time with me.”
The end of Dr. Trojanowski’s life was difficult, Dr. Lee said. He began tripping when climbing stairs, and waking in the middle of the night and wandering. After a fall the day before his birthday in December, he asked to go to the hospital, where a scan showed deep bruises pressing on his spinal cord.
He had surgery twice to remove the clots but was left paralyzed and required a ventilator. He began getting infections, and every time an infection cleared he would get infected again.
After three weeks of stasis, Dr. Trojanowski and Dr. Lee discussed his future.
“I said, ‘You are not going into hospice care and you can’t stay here forever,’” she recalled. “‘You know you will get infections, and even if you don’t you will be paralyzed from the neck down.’”
Dr. Trojanowski decided he wanted to end his life support. He asked that his ventilator tube be removed.
He died two and a half hours later, Dr. Lee said.
In addition to his wife, Dr. Trojanowski is survived by his brothers, John, Davis and Mark, and his sisters, Lynn Trojanowski, Annie Trojanowski and Janet Meyer.