Federica Palacino, Paolo Manganotti, Alberto Benussi
Frontotemporal lobar degeneration (FTLD) represents a heterogeneous group of neurodegenerative disorders with overlapping clinical, pathological, and genetic characteristics. Increasing evidence indicates that disease mechanisms begin decades before the appearance of clinical symptoms, highlighting the importance of identifying preclinical and prodromal stages. This review provides a comprehensive synthesis of current knowledge on the complexity of FTLD, emphasizing early detection and intervention strategies. It integrates findings from neuropathological, neuroimaging, fluid biomarker, genetic, and clinical studies in both familial and sporadic forms, with particular attention to gene-specific trajectories, biomarker evolution, and emerging therapeutic approaches targeting presymptomatic and prodromal phases. Recent advances in biomarker discovery and neuroimaging are enabling earlier diagnosis and intervention, offering the potential to delay phenoconversion and preserve brain function.