This issue of Acta Neuropathologica includes a cluster of four manuscripts that bear the imprint of John Q. Trojanowski, M.D., Ph.D. Having passed away just under 1 year ago, much has been written about John [1,2,3,4,5,6,7,8,9,10]. This current issue is a celebration of his enduring impact on the field of neuropathology. These four studies remind us of how scientific advances are fostered by collaboration, coordination, and counselling.

Giannini et al. describe a series of 38 cases of frontotemporal lobar degeneration with tau inclusions due to pathogenic MAPT variants, highlighting their heterogeneity in terms of the distribution and isoform composition of tau aggregates [11]. Interestingly, these changes consistently converge on the anterior temporal lobe which constantly exhibits severe neurodegeneration. This work represents a collaboration between Harro Seelaar, M.D., Ph.D., from Erasmus University Medical Center, Netherlands, and David Irwin, M.D., from the University of Pennsylvania, Philadelphia, USA where Lucia A. A. Giannini, M.D., Ph.D., served as the conduit between these two institutions. John Q. Trojanowski fostered many international collaborations and shared his resources widely to facilitate our understanding of neurodegenerative disease, particularly in instances where combining resources adds statistical power and rigor such as the study of rare genetic forms of dementia.

Continuing on the theme of rare neurodegenerative disease genetic variants, Kim et al. describe a series of 31 cases of Alzheimer’s disease associated with TREM2 risk variants [12]. As the largest clinicopathologic series of TREM2 variants to date, Boram Kim, M.D., and I found that TREM2 risk variant cases are associated with non-amnestic clinical phenotypes and hippocampal-sparing neurofibrillary degeneration. Moreover, TREM2 risk variants were associated with elevated cortical tau burden, and in turn to microglial dystrophy. This study relied solely on the materials and data available at John Trojanowski’s academic home institution, the University of Pennsylvania, representing a tremendous amount of collaboration and coordination between pathologists, geneticists, neuropsychologists and clinicians, who have freely shared their domain’s knowledge and data with each other using the infrastructure instigated by John Trojanowski decades ago.

Diversity of thought allows for the cross-fertilization of ideas. Thus, John Trojanowski fostered relationships among disparate groups, for example facilitating interactions among groups studying Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease, motor neuron disease, and others. Thus, it is noteworthy that Arezoumandan et al. describe a study focused on a deep neuropathologic phenotyping of non-amnestic Alzheimer’s disease, showing differences in neurofibrillary tangle maturity in a region-specific manner [13]. As the second study in this issue focused on atypical Alzheimer’s disease, clearly this work was influenced by those in our Frontotemporal Degeneration Center, who recognized that atypical phenotypes, often associated with FTD, are seen in cases with dementia due to Alzheimer’s disease. This is also the second study led by David Irwin, a cognitive neurologist who was mentored by John Trojanowski and who is now dedicated to neuropathology studies, applying advanced image analysis methods to derive quantitative measures which reveal how diverse neuropathologies result in the clinical phenotypes observed in his patients.

Finally, Nguyen et al. represent the leading edge of John Q. Trojanowski’s legacy. Aivi T. Nguyen, M.D., identified the neuropathologic correlates to diffuse MRI abnormalities in the setting of cerebrovascular disease [14]. John Trojanowski trained many neuropathologists and scientists, many of whom are now leaders in our field. I myself was one of his trainees and had the pleasure of working with John for nearly 25 years. Led by Melissa E. Murray, Ph.D., and Prashanthi Vemuri, Ph.D., from the Mayo Clinic, this final study did not rely on John Trojanowski’s data or infrastructure, except that Aivi Nguyen trained under John before joining my laboratory as a postdoctoral fellow. Now an independent scientist and neuropathologist at the Mayo Clinic, Aivi Nguyen represents the cascading effects that stem from counselling, mentoring, and investing in the next generation of neuropathologist–scientist. Thus, John Q. Trojanowski’s legacy continues to grow and the future of neuropathology remains bright.