The world of neurodegeneration research was saddened this week by the death of John Q. Trojanowski, MD PhD, on February 8, 2022 at age 75. He was a neuropathologist at the University of Pennsylvania.
John’s work focused on protein aggregates and mechanisms of neurodegenerative disease spread. Together with his life partner and research collaborator Dr. Virginia M-Y Lee, he played a central role in discovering the roles of tau protein in Alzheimer’s disease, of TDP-43 in frontotemporal dementia, and of alpha-synuclein in Parkinson’s disease and Lewy body dementia. A major discovery John spearheaded was to extract abnormal tau protein from the autopsied brains of people with PSP and CBD and inject it into the brains of normal mice. The animals developed PSP-like or CBD-like abnormalities, respectively, showing that the tau molecule is not a by-product of the degenerative process, but its specific cause. He also showed that the tau from the human donor’s glial cells affects only the glial cells of the mouse, concluding that glial-acting tau differs from neuronal-acting tau. That observation could have major implications for a treatment or prevention of PSP and CBD.
My own research collaboration with John occurred back in the late 1990s. I was the clinical leader of a group that in 1990 discovered the first family proven to have hereditary Parkinson’s disease. In 1997, my group collaborating with geneticists at the NIH showed that the disease in that family was caused by a mutation in alpha-synuclein, a gene not previously suspected of an association with PD. But that didn’t mean that alpha-synuclein had any significance for PD in general. Immediately after John saw our paper in Science, he got to work, finding that the Lewy bodies of ordinary PD were chock full of alpha-synuclein. Although I was not a laboratory researcher, he then involved me in his research. That team showed that the brains from affected members of the family with the alpha-synuclein mutation had not only Lewy bodies, but also tau aggregates in the form of thread-like neurites. Another paper of “ours” showed that alpha-synuclein and tau each promotes the aggregation of the other, implying that interrupting one process might interrupt the other.
I wasn’t the only one whom John generously included in his projects. He worked with top tau research groups world-wide and was welcomed as a collaborator not only for his scientific productivity, but also for his collegiality and his ability to explain difficult scientific concepts. His sense of humor and sense of style were icing on the cake.
All those fighting neurodegenerative diseases have lost a fine friend.