Biofluid-based staging of Alzheimer’s disease

Recently, conceptual systems for the in vivo staging of Alzheimer's disease (AD) using fluid biomarkers have been suggested. Thus, it is important to assess whether available fluid biomarkers can successfully stage AD into clinically and biologically relevant categories. In the TRIAD cohort, we explored whether p-tau217, p-tau205 and NTA-tau (biomarkers of early, intermediate and late AD pathology, respectively) have potential for biofluid-based staging in cerebrospinal fluid (CSF; n = 219) and plasma (n = 150), and compared them in a paired CSF and plasma subset (n = 76). Our findings suggest a good concordance between biofluid staging and underlying pathology when classifying amyloid-positivity into three categories based on neurofibrillary pathology: minimal/non-existent (p-tau217 positive), early-to-intermediate (p-tau217 and p-tau205 positivity), and advanced tau tangle deposition (p-tau217, p-tau205 and NTA-tau positive), as indexed by tau-PET. Discordant cases accounted for 4.6% and 13.3% of all CSF and plasma measurements respectively (9.2% and 11.8% in paired samples). Notably, CSF- and plasma-based staging matched one another in 61.7% of the cases, while approximately 32% of the remaining participants were one to three biofluid stages higher in CSF as compared to plasma. Overall, these exploratory results suggest that biofluid staging of AD holds potential for offering valuable insights into underlying AD hallmarks and disease severity. However, its applicability beyond molecular characterization at research settings has yet to be demonstrated.

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Publication Details

Journal
Acta Neuropathologica
Published
2025-03-17
DOI
https://doi.org/10.1007/s00401-025-02863-w
Citations
7
Primary Topic
Dementia and Cognitive Impairment Research
Type
article
Field-Weighted Citation Impact
10.30
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article

Biofluid-based staging of Alzheimer’s disease

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7 citations
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Dementia and Cognitive Impairment Research
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article

Biofluid-based staging of Alzheimer’s disease

Serge Gauthier, Tharick Ali Pascoal, Guglielmo Di Molfetta, Joseph Therriault, Paolo Vitali, Kaj Blennow, Juan Lantero‐Rodriguez, Wagner S. Brum, Jesse Klostranec, Burak Arslan, Nesrine Rahmouni, Andréa Lessa Benedet, Arthur C. Macedo, Ilaria Pola, Stijn Servaes, Laia Montoliu‐Gaya, Maxime Montembeault, Andreas Jeromin, Cécile Tissot, Pedro Rosa‐Neto, Johan Gobom, Nicholas J. Ashton, Jenna Stevenson, Henrik Zetterberg
article en
7 citations

Abstract

Recently, conceptual systems for the in vivo staging of Alzheimer's disease (AD) using fluid biomarkers have been suggested. Thus, it is important to assess whether available fluid biomarkers can successfully stage AD into clinically and biologically relevant categories. In the TRIAD cohort, we explored whether p-tau217, p-tau205 and NTA-tau (biomarkers of early, intermediate and late AD pathology, respectively) have potential for biofluid-based staging in cerebrospinal fluid (CSF; n = 219) and plasma (n = 150), and compared them in a paired CSF and plasma subset (n = 76). Our findings suggest a good concordance between biofluid staging and underlying pathology when classifying amyloid-positivity into three categories based on neurofibrillary pathology: minimal/non-existent (p-tau217 positive), early-to-intermediate (p-tau217 and p-tau205 positivity), and advanced tau tangle deposition (p-tau217, p-tau205 and NTA-tau positive), as indexed by tau-PET. Discordant cases accounted for 4.6% and 13.3% of all CSF and plasma measurements respectively (9.2% and 11.8% in paired samples). Notably, CSF- and plasma-based staging matched one another in 61.7% of the cases, while approximately 32% of the remaining participants were one to three biofluid stages higher in CSF as compared to plasma. Overall, these exploratory results suggest that biofluid staging of AD holds potential for offering valuable insights into underlying AD hallmarks and disease severity. However, its applicability beyond molecular characterization at research settings has yet to be demonstrated.

Acta NeuropathologicaVol. 149(1)
Universidade Federal do Rio Grande (BR), Montreal Neurological Institute and Hospital (CA), Universidade Federal do Rio Grande do Sul (BR), University of Wisconsin–Madison (US), Lawrence Berkeley National Laboratory (US), University of Pittsburgh (US), King's College London (GB), Sahlgrenska University Hospital (SE), Centre for Mental Health (GB), UK Dementia Research Institute (GB), National Hospital for Neurology and Neurosurgery (GB), University College London (GB), McGill University (CA), University of Gothenburg (SE)
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Openalex Percentile: Top 2%
Dementia and Cognitive Impairment Research
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