Concordance of Lumipulse cerebrospinal fluid t‐tau/Aβ42 ratio with amyloid PET status
Open accessAbstract
Introduction: Cerebrospinal fluid (CSF) biomarkers can identify individuals with Alzheimer's disease (AD) pathology (eg, amyloid plaques, neurofibrillary tangles), but defined analyte cut‐points using high‐throughput automated assays are necessary for general clinical use. Methods: CSF amyloid β42 peptide (Aβ42), t‐tau, and t‐tau/Aβ42 were quantified by the Lumipulse platform in two test cohorts (A/B: Eisai BAN2401‐201/MISSION AD E2609‐301/302, n = 138; C: Knight Alzheimer's Disease Research Center (ADRC), n = 198), and receiver operating characteristic (ROC) curve analyses defined cut‐points corresponding best to amyloid determinations using positron emission tomography (PET) imaging. The best‐performing cut‐point was then validated as a predictor of amyloid status in an independent cohort (D: MISSION AD E2609‐301/302, n = 240). Results: Virtually identical t‐tau/Aβ42 cut‐points (∼0.54) performed best in both test cohorts and with similar accuracy (areas under ROC curve [AUCs] [A/B: 0.95; C: 0.94]). The cut‐point yielded an overall percent agreement with amyloid PET of 85.0% in validation cohort D. Discussion: Lumipulse CSF biomarker measures with validated cut‐points have clinical utility in identifying AD pathology.
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The two-cutoffs approach is currently employed for the FDA-approved CSF Lumipulse test and has been suggested for AD blood-based biomarkers, especially when very high accuracy is needed.
“Notably, the two-cutoffs approach is currently employed for the FDA-approved CSF Lumipulse test42,43 and has been suggested for AD BBMs17,55, especially when very high accuracy is needed.”
From Highly accurate blood test for Alzheimer's disease is similar or superior to clinical cerebrospinal fluid tests (2024) · cites this paper as [43]
The Results section (‘CSF biomarker cut-points for distinguishing amyloid PET status’; page unavailable) reports one selected t-tau/Aβ42 threshold, not a two-cutoffs approach. The Introduction also states that no CSF biomarker assay was FDA-cleared at the time of this study. That historical statement cannot establish the test’s current approval status, but this paper does not support the approach attributed to it. (LLM, conf=0.87)
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“Notably, the two-cutoffs approach is currently employed for the FDA-approved CSF Lumipulse test 42,43 and has been suggested for AD BBMs 17,55 , especially when very high accuracy is needed.”
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“T-tau/ Aβ42 > 0.54 was considered positive for AD pathology [32].”
BackgroundInfluential
- Authors
- Kaplow, J., Vandijck, M., Gray, J., Kanekiyo, M., Huyck, E., Traynham, C. J., Esquivel, R., Fagan, A. M., & Luthman, J.
- Affiliations
- Eisai (United States) (US)
- Fujirebio (Belgium) (BE)
- Washington University in St. Louis (US)
- Fujirebio US (United States) (US)
- Corresponding author
- Fagan, Anne M.
- Luthman, Johan
- ORCID
- Fagan, Anne M.
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2020-01
- Volume
- 16
- Issue
- 1
- Pages
- 144-152
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC7061432
- OpenAlex
- W2999349682
- Cited by
- 81
- References
- 11
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 21 · 2023: 15 · 2022: 13 · 2021: 18 · 2020: 2
- FWCI
- 8.76
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH National Institute on Aging (P01AG026276, P01AG03991, P50AG05681)
- Barnes Jewish Hospital Foundation (P30NS098577, R01EB009352, UL1TR000448)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, cerebrospinal fluid biomarkers
- MeSH terms
- Aged, Alzheimer Disease, Amyloid, Female, Humans, Male, Middle Aged, Peptide Fragments, Reproducibility of Results, Cohort Studies, Biomarkers, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography
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