This paper proposes a pathobiology-based framework for classifying TDP-43–associated neurodegenerative diseases — including LATE, ALS, FTD, inclusion body myositis, and multisystem proteinopathy — shifting away from clinical phenotype as the organizing principle and introducing an integrated staging system that accounts for presymptomatic disease.
The authors argue that TDP-43 pathology underlies a spectrum of clinically distinct disorders and that recognizing this shared biology — with clinical labels like ALS, FTD, or LATE recast as phenotypic manifestations — provides a clearer road map for biomarker development and therapy targeting fundamental disease mechanisms.
This is a conceptual/opinion paper without primary data; no clinical outcomes, biomarker validation cohorts, or staging criteria are empirically tested here.
Clinicians should be aware that ALS, FTD, LATE, and related disorders may share a common TDP-43 pathobiology, which has direct implications for how future biomarkers and disease-modifying therapies will be developed and trialed across these conditions.
