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A two-step workflow...
A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases
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- Brum, Wagner S. (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Federal University of Rio Grande do Sul,Sahlgrenska Academy,McGill University Research Centre for Studies in Aging
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- Cullen, Nicholas C. (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Janelidze, Shorena (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas
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- Ashton, Nicholas J. (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Stavanger University Hospital,Sahlgrenska Academy,King's College London,South London and Maudsley NHS Foundation Trust
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- Zimmer, E. R. (author)
- Federal University of Rio Grande do Sul,McGill University Research Centre for Studies in Aging
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- Therriault, J. (author)
- McGill University Research Centre for Studies in Aging,McGill University
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- Lessa Benedet, Andréa (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska Academy
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- Rahmouni, N. (author)
- McGill University Research Centre for Studies in Aging,McGill University
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- Tissot, C. (author)
- McGill University Research Centre for Studies in Aging,McGill University
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- Stevenson, J. (author)
- McGill University,McGill University Research Centre for Studies in Aging
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Servaes, S. (author)
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- Triana-Baltzer, G. (author)
- Janssen Research & Development, Belgium
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- Kolb, H. C. (author)
- Janssen Research & Development, Belgium
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- Palmqvist, Sebastian (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital
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- Stomrud, Erik (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital
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- Rosa-Neto, P. (author)
- McGill University Research Centre for Studies in Aging,McGill University
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska Academy,Sahlgrenska University Hospital
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- Hansson, Oskar (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Nature Aging. - 2662-8465. ; 3:9, s. 1079-1090
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Abstract
Subject headings
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- Cost-effective strategies for identifying amyloid-beta (A beta) positivity in patients with cognitive impairment are urgently needed with recent approvals of anti-A beta immunotherapies for Alzheimer's disease (AD). Blood biomarkers can accurately detect AD pathology, but it is unclear whether their incorporation into a full diagnostic workflow can reduce the number of confirmatory cerebrospinal fluid (CSF) or positron emission tomography (PET) tests needed while accurately classifying patients. We evaluated a two-step workflow for determining A beta-PET status in patients with mild cognitive impairment (MCI) from two independent memory clinic-based cohorts (n = 348). A blood-based model including plasma tau protein 217 (p-tau217), age and APOE epsilon 4 status was developed in BioFINDER-1 (area under the curve (AUC) = 89.3%) and validated in BioFINDER-2 (AUC = 94.3%). In step 1, the blood-based model was used to stratify the patients into low, intermediate or high risk of A beta-PET positivity. In step 2, we assumed referral only of intermediate-risk patients to CSF A beta 42/A beta 40 testing, whereas step 1 alone determined A beta-status for low-and high-risk groups. Depending on whether lenient, moderate or stringent thresholds were used in step 1, the two-step workflow overall accuracy for detecting A beta-PET status was 88.2%, 90.5% and 92.0%, respectively, while reducing the number of necessary CSF tests by 85.9%, 72.7% and 61.2%, respectively. In secondary analyses, an adapted version of the BioFINDER-1 model led to successful validation of the two-step workflow with a different plasma p-tau217 immunoassay in patients with cognitive impairment from the TRIAD cohort (n = 84). In conclusion, using a plasma p-tau217-based model for risk stratification of patients with MCI can substantially reduce the need for confirmatory testing while accurately classifying patients, offering a cost-effective strategy to detect AD in memory clinic settings.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- alzheimers-disease
- apolipoprotein-e
- performance
- validation
- epsilon-4
- diagnosis
- biomarker
- selection
- age
- Cell Biology
- Geriatrics & Gerontology
- Neurosciences & Neurology
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Brum, Wagner S.
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Cullen, Nicholas ...
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Janelidze, Shore ...
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Ashton, Nicholas ...
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Zimmer, E. R.
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Therriault, J.
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show more...
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Lessa Benedet, A ...
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Rahmouni, N.
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Tissot, C.
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Stevenson, J.
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Servaes, S.
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Triana-Baltzer, ...
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Kolb, H. C.
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Palmqvist, Sebas ...
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Stomrud, Erik
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Rosa-Neto, P.
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Blennow, Kaj, 19 ...
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Hansson, Oskar
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
- Articles in the publication
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Nature Aging
- Nature Aging
- By the university
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University of Gothenburg
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Lund University