New developments of biofluid-based biomarkers for routine diagnosis and disease trajectories in frontotemporal dementia

Altres ajuts: The Swedish Research Council (#2018-02532); Swedish State Support for Clinical Research (#ALFGBG-720931); the Alzheimer Drug Discovery Foundation (ADDF) (#201809-2016862); the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C, #ADSF-21-831377-C); the Olav Thon Foundation; the Erling-Persson Family Foundation; Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228); the UK Dementia Research Institute at UCL; The Robert and Nancy Hall Brain Research Fund. Frontotemporal dementia (FTD) covers a spectrum of neurodegenerative disorders with different phenotypes, genetic backgrounds, and pathological states. Its clinicopathological diversity challenges the diagnostic process and the execution of clinical trials, calling for specific diagnostic biomarkers of pathologic FTD types. There is also a need for biomarkers that facilitate disease staging, quantification of severity, monitoring in clinics and observational studies, and for evaluation of target engagement and treatment response in clinical trials. This review discusses current FTD biofluid-based biomarker knowledge taking into account the differing applications. The limitations, knowledge gaps, and challenges for the development and implementation of such markers are also examined. Strategies to overcome these hurdles are proposed, including the technologies available, patient cohorts, and collaborative research initiatives. Access to robust and reliable biomarkers that define the exact underlying pathophysiological FTD process will meet the needs for specific diagnosis, disease quantitation, clinical monitoring, and treatment development.