Producción CyT
Congreso
Autoría
Weissmann, Carina
;
SALINAS CASTELLANOS, LIBIA CATALINA
;
Montes, Mayra Micaela
;
Uruk, Gokhan
;
Youssef, Hossam
;
Reichard, R. Ross
;
Josephs, Keith A
;
Gatto, Rodolfo G.
Fecha
2025
Editorial y Lugar de Edición
HAI
Resumen
Información suministrada por el agente en
SIGEVA
Introduction: We previously evaluated the [¹⁸F]flortaucipir (FTP) analog T726 and demonstrated its colocalization with paired helical filament (PHF) tau, along with partial binding to both 3-repeat (3R) and 4-repeat (4R) tau isoforms in frontotemporal lobar degeneration (FTLD). These findings suggested that FTP may have broader binding capabilities, potentially extending to other proteinopathies. Given that FTP uptake has been indentified in cases of frontotemporal lobar degeneration...
Introduction: We previously evaluated the [¹⁸F]flortaucipir (FTP) analog T726 and demonstrated its colocalization with paired helical filament (PHF) tau, along with partial binding to both 3-repeat (3R) and 4-repeat (4R) tau isoforms in frontotemporal lobar degeneration (FTLD). These findings suggested that FTP may have broader binding capabilities, potentially extending to other proteinopathies. Given that FTP uptake has been indentified in cases of frontotemporal lobar degeneration with phosphorylated TAR DNA-binding protein 43 (pTDP-43) (FTLD-TDP), we sought to investigate whether T726 is also capable of binding to pTDP-43 aggregates in vitro.Materials and Methods: To assess this, HEK cells were transfected with a plasmid encoding mCherry-tagged TDP-43 under conditions that promote aggregation. Additionally, control experiments were performed to confirm specificity of T726 binding. T726 immunofluorescence was evaluated in multiple experimental conditions: cells expressing mCherry-TDP-43 with and without aggregates, cells expressing mCherry alone, and cells containing aggregates of an unrelated protein (fluorescently tagged huntingtin). In parallel, representative human brain samples from Alzheimer’s disease patients with TDP-43 pathology and FTLD-TDP cases (temporal and hippocampal regions) were examined using fluorescence immunohistochemistry with pTDP-43 antibodies and co-incubation with T726 to assess colocalization and regional distribution.Results: T726 fluorescence was observed exclusively in cells exhibiting mCherry-TDP-43 aggregation, with no signal detected in control conditions. In human tissue samples, T726 colocalized with pTDP-43 pathology across limbic regions in both AD+pTDP-43 and FTLD-TDP cases. Conclusions: These findings suggest that FTP may bind to pTDP-43 aggregates in cases of FTLD-TDP, and potentially to pTDP-43 in AD+pTDP-43 cases as well. Future studies are planned to further characterize these molecular interactions and assess their representation in human samples.
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Palabras Clave
FTLDT726ADTDP-43