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Biomarkers that accurately predict amyloid-\u03b2 accumulation may be of critical importance for participant inclusion in secondary prevention trials and thus enhance development of early Alzheimer\u2019s disease therapies. We compared the abilities of baseline plasma pTau181, pTau217 and amyloid-\u03b2 PET load to predict future amyloid-\u03b2 accumulation in asymptomatic elderly. In this longitudinal cohort study, baseline plasma pTau181 and pTau217 were quantified using single molecule array assays in cognitively unimpaired elderly selected from the community-recruited F-PACK cohort based on the availability of baseline plasma samples and longitudinal amyloid-\u03b2 PET data (median time interval = 5 years, range 2\u201310 years). The predictive abilities of pTau181, pTau217 and PET-based amyloid-\u03b2 measures for PET-based amyloid-\u03b2 accumulation were investigated using receiver operating characteristic analyses, correlations and stepwise regression analyses. We included 75 F-PACK subjects (mean age = 70 years, 48% female), of which 16 were classified as amyloid-\u03b2 accumulators [median (interquartile range) Centiloid rate of change = 3.42 (1.60) Centiloids\/year). Plasma pTau181 [area under the curve (95% confidence interval) = 0.72 (0.59\u20130.86)] distinguished amyloid-\u03b2 accumulators from non-accumulators with similar accuracy as pTau217 [area under the curve (95% confidence interval) = 0.75 (0.62\u20130.88) and amyloid-\u03b2 PET [area under the curve (95% confidence interval) = 0.72 (0.56\u20130.87)]. Plasma pTau181 and pTau217 strongly correlated with each other (r = 0.93, Pfalse discovery rate &amp;lt; 0.001) and, together with amyloid-\u03b2 PET, similarly correlated with amyloid-\u03b2 rate of change (rpTau181 = 0.33, rpTau217 = 0.36, ramyloid-\u03b2 PET = 0.35, all Pfalse discovery rate \u2264 0.01). Addition of plasma pTau181, plasma pTau217 or amyloid-\u03b2 PET to a linear demographic model including age, sex and APOE-\u03b54 carriership similarly improved the prediction of amyloid-\u03b2 accumulation (\u0394Akaike information criterion \u2264 4.1). In a multimodal biomarker model including all three biomarkers, each biomarker lost their individual predictive ability. These findings indicate that plasma pTau181, plasma pTau217 and amyloid-\u03b2 PET convey overlapping information and therefore predict the dynamic phase of asymptomatic amyloid-\u03b2 accumulation with comparable performances. In clinical trial recruitment, confirmatory PET scans following blood-based prescreening might thus not provide additional value for detecting participants in these early disease stages who are destined to accumulate cortical amyloid-\u03b2. Given the moderate performances, future studies should investigate whether integrating plasma pTau species with other factors can improve performance and thus enhance clinical and research utility.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae162","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T16:49:13Z","timestamp":1716396553000},"source":"Crossref","is-referenced-by-count":30,"title":["Plasma pTau181 and pTau217 predict asymptomatic amyloid accumulation equally well as amyloid PET"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6729-7601","authenticated-orcid":false,"given":"Steffi","family":"De Meyer","sequence":"first","affiliation":[{"name":"Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven , 3000 Leuven ,","place":["Belgium"]},{"name":"Laboratory for Molecular Neurobiomarker Research, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolien M","family":"Schaeverbeke","sequence":"additional","affiliation":[{"name":"Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1777-4742","authenticated-orcid":false,"given":"Emma S","family":"Luckett","sequence":"additional","affiliation":[{"name":"Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven , 3000 Leuven ,","place":["Belgium"]},{"name":"Laboratory for Complex Genetics, Department of Human Genetics, KU Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7964-7963","authenticated-orcid":false,"given":"Mariska","family":"Reinartz","sequence":"additional","affiliation":[{"name":"Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena R","family":"Blujdea","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Clinical Chemistry, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc , 1081 HV Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0857-7683","authenticated-orcid":false,"given":"Isabelle","family":"Cleynen","sequence":"additional","affiliation":[{"name":"Laboratory for Complex Genetics, Department of Human Genetics, KU Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Dupont","sequence":"additional","affiliation":[{"name":"Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen","family":"Van Laere","sequence":"additional","affiliation":[{"name":"Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven , 3000 Leuven ,","place":["Belgium"]},{"name":"Division of Nuclear Medicine, UZ Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Vanbrabant","sequence":"additional","affiliation":[{"name":"ADx NeuroSciences NV , 9052 Ghent ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Stoops","sequence":"additional","affiliation":[{"name":"ADx NeuroSciences NV , 9052 Ghent ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugeen","family":"Vanmechelen","sequence":"additional","affiliation":[{"name":"ADx NeuroSciences NV , 9052 Ghent ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guglielmo","family":"di Molfetta","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg , S-431 80 M\u00f6lndal ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg , S-431 80 M\u00f6lndal ,","place":["Sweden"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , S-431 80 M\u00f6lndal ,","place":["Sweden"]},{"name":"Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square , WC1N 3BG London ,","place":["UK"]},{"name":"UK Dementia Research Institute at UCL , WC1N 3BG London ,","place":["UK"]},{"name":"Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay , Hong Kong ,","place":["China"]},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI 53792 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J","family":"Ashton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg , S-431 80 M\u00f6lndal ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4061-0837","authenticated-orcid":false,"given":"Charlotte E","family":"Teunissen","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Clinical Chemistry, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc , 1081 HV Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5290-9476","authenticated-orcid":false,"given":"Koen","family":"Poesen","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neurobiomarker Research, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven , 3000 Leuven ,","place":["Belgium"]},{"name":"Laboratory Medicine Department, UZ Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6237-2502","authenticated-orcid":false,"given":"Rik","family":"Vandenberghe","sequence":"additional","affiliation":[{"name":"Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven , 3000 Leuven ,","place":["Belgium"]},{"name":"Neurology Department, UZ Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,23]]},"reference":[{"issue":"5054","key":"2025070208213600500_fcae162-B1","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1126\/science.1566067","article-title":"Alzheimer\u2019s disease: The amyloid cascade hypothesis","volume":"256","author":"Hardy","year":"1992","journal-title":"Science"},{"issue":"6738 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