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Fluid biomarkers for neurodegenerative diseases : a comprehensive update

Valletta, Martina ; Briel, Nils ; Yuksekel, Idil ; Barboure, Michelle ; Coward, Anna ; De Houwer, Julie F.H. ; Fawad, Ayesha LU orcid ; González-Mayoral, Alberto ; Iaccarino, Gianmarco and Martínez-Dubarbie, Francisco , et al. (2026) In Alzheimer's Research and Therapy 18(1).
Abstract

Fluid biomarkers are revolutionizing the diagnosis and management of neurodegenerative diseases by enabling earlier diagnosis and disease monitoring. In particular, blood-based biomarkers have emerged as a minimally invasive and scalable alternative to cerebrospinal fluid analysis. Recent advances in blood-based tau biomarkers have shown high diagnostic accuracy for Alzheimer’s disease (AD). Other neurodegenerative diseases—such as synucleinopathies, frontotemporal lobar degeneration, limbic-predominant age-related TDP-43 encephalopathy (LATE), and amyotrophic lateral sclerosis—pose substantial challenges due to their heterogeneous clinical presentations and the current absence of robust biomarkers for hallmark pathologies. Nonetheless,... (More)

Fluid biomarkers are revolutionizing the diagnosis and management of neurodegenerative diseases by enabling earlier diagnosis and disease monitoring. In particular, blood-based biomarkers have emerged as a minimally invasive and scalable alternative to cerebrospinal fluid analysis. Recent advances in blood-based tau biomarkers have shown high diagnostic accuracy for Alzheimer’s disease (AD). Other neurodegenerative diseases—such as synucleinopathies, frontotemporal lobar degeneration, limbic-predominant age-related TDP-43 encephalopathy (LATE), and amyotrophic lateral sclerosis—pose substantial challenges due to their heterogeneous clinical presentations and the current absence of robust biomarkers for hallmark pathologies. Nonetheless, promising candidate markers are emerging for improved disease characterization and staging. Technological innovations, including single-molecule arrays (Simoa), advanced mass spectrometry workflows and nucleic acid linked immune-sandwich assay (NULISA) have markedly enhanced the sensitivity and precision of biomarker quantification from low-concentration biological matrices. More recently, the development of fully automated platforms shows great promise for routine measurement of blood-based biomarkers in clinical settings. Despite this progress key challenges remain, including the need for improved assay reproducibility, standardization, and the optimization of clinical workflows. In this review, we provide a comprehensive update on recent progress in fluid biomarker research across AD and major neurodegenerative diseases, highlight technological advances in detection methods, and discuss current challenges and opportunities for clinical translation.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's Disease, Blood-Based Biomarkers, CSF Biomarkers, Fluid Biomarkers, Glial Fibrillary Acidic Protein, Neurodegeneration, Neurofilament Light Chain, Synuclein, Tau, TDP-43
in
Alzheimer's Research and Therapy
volume
18
issue
1
article number
12
publisher
BioMed Central (BMC)
external identifiers
  • pmid:41422050
  • scopus:105027534161
ISSN
1758-9193
DOI
10.1186/s13195-025-01919-z
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2025.
id
bf92fca0-b8a6-4bc4-8328-db2df1f297c8
date added to LUP
2026-03-09 14:30:43
date last changed
2026-04-09 13:09:51
@article{bf92fca0-b8a6-4bc4-8328-db2df1f297c8,
  abstract     = {{<p>Fluid biomarkers are revolutionizing the diagnosis and management of neurodegenerative diseases by enabling earlier diagnosis and disease monitoring. In particular, blood-based biomarkers have emerged as a minimally invasive and scalable alternative to cerebrospinal fluid analysis. Recent advances in blood-based tau biomarkers have shown high diagnostic accuracy for Alzheimer’s disease (AD). Other neurodegenerative diseases—such as synucleinopathies, frontotemporal lobar degeneration, limbic-predominant age-related TDP-43 encephalopathy (LATE), and amyotrophic lateral sclerosis—pose substantial challenges due to their heterogeneous clinical presentations and the current absence of robust biomarkers for hallmark pathologies. Nonetheless, promising candidate markers are emerging for improved disease characterization and staging. Technological innovations, including single-molecule arrays (Simoa), advanced mass spectrometry workflows and nucleic acid linked immune-sandwich assay (NULISA) have markedly enhanced the sensitivity and precision of biomarker quantification from low-concentration biological matrices. More recently, the development of fully automated platforms shows great promise for routine measurement of blood-based biomarkers in clinical settings. Despite this progress key challenges remain, including the need for improved assay reproducibility, standardization, and the optimization of clinical workflows. In this review, we provide a comprehensive update on recent progress in fluid biomarker research across AD and major neurodegenerative diseases, highlight technological advances in detection methods, and discuss current challenges and opportunities for clinical translation.</p>}},
  author       = {{Valletta, Martina and Briel, Nils and Yuksekel, Idil and Barboure, Michelle and Coward, Anna and De Houwer, Julie F.H. and Fawad, Ayesha and González-Mayoral, Alberto and Iaccarino, Gianmarco and Martínez-Dubarbie, Francisco and Moukaled, Shirine and Andreasson, Ulf and Gobom, Johan and Brinkmalm, Ann and Tijms, Betty and Zetterberg, Henrik and Blennow, Kaj and Suárez-Calvet, Marc and Schöll, Michael and Paterson, Ross W. and Montoliu-Gaya, Laia and Sogorb-Esteve, Aitana}},
  issn         = {{1758-9193}},
  keywords     = {{Alzheimer's Disease; Blood-Based Biomarkers; CSF Biomarkers; Fluid Biomarkers; Glial Fibrillary Acidic Protein; Neurodegeneration; Neurofilament Light Chain; Synuclein; Tau; TDP-43}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Alzheimer's Research and Therapy}},
  title        = {{Fluid biomarkers for neurodegenerative diseases : a comprehensive update}},
  url          = {{http://dx.doi.org/10.1186/s13195-025-01919-z}},
  doi          = {{10.1186/s13195-025-01919-z}},
  volume       = {{18}},
  year         = {{2026}},
}