Evidence map›Paper›PMID 38514824›Full record

ArticleNature aging2024

Disease staging of Alzheimer's disease using a CSF-based biomarker model.

Gemma Salvadó, Kanta Horie, Nicolas R Barthélemy, Jacob W Vogel, Alexa Pichet Binette, Charles D Chen, Andrew J Aschenbrenner, Brian A Gordon, Tammie L S Benzinger, David M Holtzman and 8 more

Abstract read
In one paragraph

Article in Nature aging, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
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  6. Article
  7. Article
  8. Tau-PET and CSF MTBR-tau243 comparisons validate increased tau aggregation in females.European journal of nuclear medicine and molecular imaging · 2026
    Article
  9. Article
  10. Observational
  11. Relationships of CSF biomarkers to cortical atrophy in early-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
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  20. Review

22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Gemma SalvadóClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden. gemma.salvado@med.lu.se.ORCID http://orcid.org/0000-0002-5210-9230
Kanta HorieTracy Family Stable Isotope Labeling Quantitation (SILQ) Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-7736-2614
Nicolas R BarthélemyTracy Family Stable Isotope Labeling Quantitation (SILQ) Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-4937-2860
Jacob W VogelClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0001-6394-9940
Alexa Pichet BinetteClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0001-5218-3337
Charles D ChenDepartment of Radiology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-6698-1268
Andrew J AschenbrennerDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Brian A GordonDepartment of Radiology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-2109-2955
Tammie L S BenzingerDepartment of Radiology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-8114-0552
David M HoltzmanDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
John C MorrisDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Sebastian PalmqvistClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0002-9267-1930
Erik StomrudClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Shorena JanelidzeClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0003-2869-8378
Rik OssenkoppeleClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Suzanne E SchindlerDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Randall J BatemanTracy Family Stable Isotope Labeling Quantitation (SILQ) Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-7729-1702
Oskar HanssonClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden. oskar.hansson@med.lu.se.ORCID http://orcid.org/0000-0001-8467-7286

Funding

Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
The natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5M
Research Education ComponentP30AG066444 · NIA · WASHINGTON UNIVERSITY · PI DAVID M. HOLTZMAN · 2020 to 2026
$28.7M
Staging Alzheimer disease with blood-based biomarkersR01AG070941 · NIA · WASHINGTON UNIVERSITY · PI SCHINDLER, SUZANNE ELIZABETH · 2021 to 2025
$4.3M
Multidisciplinary Training in Alzheimer and Related DementiasT32AG058518 · NIA · WASHINGTON UNIVERSITY · PI Eric Martin McDade, Barbara Joy Snider · 2018 to 2026
$2.3M
Prospective validation and implementation of high-performing blood biomarkers and digital cognitive tests for detection of Alzheimer's disease in specialist memory clinic and primary care settingsR01AG083740 · NIA · LUNDS UNIVERSITET · PI Sebastian Palmqvist · 2023 to 2026
$1.9M
NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG066444NIA NIH HHS R01 AG070941NIA NIH HHS R01 AG083740NIA NIH HHS T32 AG058518
6 · The paper itself

Abstract

Biological staging of individuals with Alzheimer's disease (AD) may improve diagnostic and prognostic workup of dementia in clinical practice and the design of clinical trials. In this study, we used the Subtype and Stage Inference (SuStaIn) algorithm to establish a robust biological staging model for AD using cerebrospinal fluid (CSF) biomarkers. Our analysis involved 426 participants from BioFINDER-2 and was validated in 222 participants from the Knight Alzheimer Disease Research Center cohort. SuStaIn identified a singular biomarker sequence and revealed that five CSF biomarkers effectively constituted a reliable staging model (ordered: Aβ42/40, pT217/T217, pT205/T205, MTBR-tau243 and non-phosphorylated mid-region tau). The CSF stages (0-5) demonstrated a correlation with increased abnormalities in other AD-related biomarkers, such as Aβ-PET and tau-PET, and aligned with longitudinal biomarker changes reflective of AD progression. Higher CSF stages at baseline were associated with an elevated hazard ratio of clinical decline. This study highlights a common molecular pathway underlying AD pathophysiology across all patients, suggesting that a single CSF collection can accurately indicate the presence of AD pathologies and characterize the stage of disease progression. The proposed staging model has implications for enhancing diagnostic and prognostic assessments in both clinical practice and the design of clinical trials.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesBiomarkerstau ProteinsAgedAlgorithmsDisease ProgressionFemaleHumansMaleMiddle AgedPeptide FragmentsPositron-Emission TomographyAmyloid beta-PeptidesBiomarkersPeptide Fragmentstau Proteins

Identifiers

PMID38514824
PMCPMC11108782

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.