RT Journal Article SR Electronic T1 Concurrent tau pathologies in frontotemporal lobar degeneration with TDP-43 pathology JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.09.23.461523 DO 10.1101/2021.09.23.461523 A1 Shunsuke Koga A1 Xiaolai Zhou A1 Aya Murakami A1 Cristhoper Fernandez De Castro A1 Matthew C. Baker A1 Rosa Rademakers A1 Dennis W. Dickson YR 2021 UL http://biorxiv.org/content/early/2021/09/24/2021.09.23.461523.abstract AB Aims Accumulating evidence suggests that patients with frontotemporal lobar degeneration (FTLD) can have pathologic accumulation of multiple proteins, including tau and TDP-43. This study aimed to determine the frequency and characteristics of concurrent tau pathology in FTLD with TDP-43 pathology (FTLD-TDP).Methods The study included 146 autopsy-confirmed cases of FTLD-TDP and 55 cases of FTLD-TDP with motor neuron disease (FTLD-MND). Sections from the basal forebrain were screened for tau pathology with phospho-tau immunohistochemistry. For cases with tau pathology on the screening section, additional brain sections were studied to establish a diagnosis. Genetic analysis of C9ORF72, GRN, and MAPT was performed on select cases.Results Among 201 cases, we found 72 cases (36%) with primary age-related tauopathy (PART), 85 (42%) with aging-related tau astrogliopathy (ARTAG), 45 (22%) with argyrophilic grain disease (AGD), and 2 cases (1%) with corticobasal degeneration (CBD). Patients with ARTAG or AGD were significantly older than those without these comorbidities. One of the patients with FTLD-TDP and CBD had C9ORF72 mutation and relatively mild tau pathology, consistent with incidental CBD.Conclusion The coexistence of TDP-43 and tau pathologies was relatively common, particularly PART and ARTAG. Although rare, individual patients with FTLD can have multiple concurrent proteinopathies. The absence of TDP-43-positive astrocytic plaques may suggest that CBD and FTLD-TDP were independent disease processes in the two patients with both tau and TDP-43 pathologies. It remains to be determined if mixed cases represent a unique disease process or two concurrent disease processes in an individual.Competing Interest StatementThe authors have declared no competing interest.