Fluid Biomarkers in Neurodegeneration: Revolutionizing Early Detection and Prognosis

Over the past decade, fluid biomarkers have transformed the conceptual and clinical framework of neurodegenerative diseases. In Alzheimer’s disease (AD), cerebrospinal fluid (CSF) measures of amyloid-β peptides, phosphorylated tau, and total tau, together with emerging blood-based biomarkers such as plasma p-tau isoforms, neurofilament light chain (NfL), and glial markers, have moved from research settings toward clinical implementation. This shift has enabled the transition from a purely syndromic diagnosis to a biologically defined disease model, as reflected in the AT(N) framework. The AD model demonstrates that neurodegeneration can be detected years before clinical symptoms emerge, opening new opportunities for early intervention and disease-modifying therapies. Importantly, this paradigm is now extending beyond AD, influencing biomarker research in other neurodegenerative disorders related to aging, including Parkinson’s disease, frontotemporal dementia, and atypical parkinsonisms.

Despite major advances, several challenges remain in translating fluid biomarkers into routine clinical practice across the spectrum of neurodegenerative diseases. Standardization across laboratories, assay harmonization, definition of validated cut-offs, and integration with imaging and clinical measures are ongoing issues. Furthermore, while AD provides a proof-of-concept for a biologically grounded classification system, similar frameworks are still under development for other proteinopathies.

An additional critical challenge concerns the integration and interpretation of cognitive measures within biomarker-driven models. While global cognitive screening tools (e.g., MMSE, MoCA) are widely used, they may not fully capture the complexity and domain-specific nature of cognitive decline in neurodegenerative diseases. This Research Topic emphasizes the importance of using nuanced, domain-sensitive cognitive metrics, including composite scores, longitudinal cognitive trajectories, and digital or high-resolution cognitive assessments as a counterpart to biological characterization. When global screening measures are employed, authors should clearly justify their adequacy in representing cognition within the context of their study. We encourage contributions that adopt rigorous and sensitive cognitive phenotyping approaches aligned with underlying biological processes.
This Research Topic aims to address these challenges by promoting interdisciplinary dialogue on how fluid biomarkers can redefine early detection, patient stratification, and prognosis in neurodegeneration. We seek to explore recent advances in ultra-sensitive detection platforms, plasma-based assays, longitudinal cohort studies, and multimodal biomarker integration. Special attention will be given to how the Alzheimer’s disease model teaches us that the future approach to neurodegenerative disorders will increasingly move from a syndromic perspective to an integrated clinical-biological model, enabling precision medicine strategies and earlier therapeutic intervention.

Topics of interest include, but are not limited to:
- Blood- and CSF-based biomarkers in Alzheimer’s disease and non-Alzheimer neurodegeneration
- Biomarker-driven disease classification models
- Longitudinal biomarker trajectories and preclinical detection
- Standardization, validation, and clinical implementation challenges
- Integration of fluid biomarkers with neuroimaging, advanced cognitive metrics, and digital biomarkers
- Methodological approaches to cognitive phenotyping in biomarker studies, including justification of cognitive measures used
- Biomarkers in clinical trials and therapeutic monitoring

We encourage submission of Original Research articles, Reviews, Systematic Reviews, Mini-Reviews, Perspectives, and methodological papers. Contributions bridging basic science and clinical application are particularly welcome, with emphasis on translational impact, precision medicine approaches, and rigorous integration of cognitive and biological measures in aging neuroscience.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Biomarkers; Neurodegeneration; Intervention; Diagnosis

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.