A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases.

Autor: Brum WS; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. wagner.scheeren.brum@gu.se.; Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. wagner.scheeren.brum@gu.se., Cullen NC; Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden., Janelidze S; Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden., Ashton NJ; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience, King's College London, London, UK.; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia, South London and Maudsley NHS Foundation, London, UK.; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway., Zimmer ER; Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.; Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.; Graduate Program in Biological Sciences: Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.; McGill Centre for Studies in Aging, McGill University, Montreal, Québec, Canada., Therriault J; Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Québec, Canada.; Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Québec, Canada., Benedet AL; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden., Rahmouni N; Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Québec, Canada.; Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Québec, Canada., Tissot C; Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Québec, Canada.; Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Québec, Canada., Stevenson J; Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Québec, Canada.; Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Québec, Canada., Servaes S; Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Québec, Canada.; Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Québec, Canada., Triana-Baltzer G; Neuroscience Biomarkers, Janssen Research & Development, La Jolla, CA, USA., Kolb HC; Neuroscience Biomarkers, Janssen Research & Development, La Jolla, CA, USA., Palmqvist S; Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.; Memory Clinic, Skåne University Hospital, Malmö, Sweden., Stomrud E; Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.; Memory Clinic, Skåne University Hospital, Malmö, Sweden., Rosa-Neto P; Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Québec, Canada.; Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Québec, Canada., Blennow K; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden., Hansson O; Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden. oskar.hansson@med.lu.se.; Memory Clinic, Skåne University Hospital, Malmö, Sweden. oskar.hansson@med.lu.se.
Jazyk: angličtina
Zdroj: Nature aging [Nat Aging] 2023 Sep; Vol. 3 (9), pp. 1079-1090. Date of Electronic Publication: 2023 Aug 31.
DOI: 10.1038/s43587-023-00471-5
Abstrakt: Cost-effective strategies for identifying amyloid-β (Aβ) positivity in patients with cognitive impairment are urgently needed with recent approvals of anti-Aβ 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 Aβ-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 ε4 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 Aβ-PET positivity. In step 2, we assumed referral only of intermediate-risk patients to CSF Aβ42/Aβ40 testing, whereas step 1 alone determined Aβ-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 Aβ-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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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