Time-encoded ASL reveals lower cerebral blood flow in the early AD continuum

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• dc.contributor.author Falcón, Carles
• dc.contributor.author Minguillón, Carolina
• dc.contributor.author Fauria, Karine
• dc.contributor.author Cascales Lahoz, Diego
• dc.contributor.author Contador, Jose
• dc.contributor.author Fernández-Lebrero, Aida
• dc.contributor.author Navalpotro-Gómez, Irene
• dc.contributor.author Puig-Pijoan, Albert
• dc.contributor.author Grau-Rivera, Oriol
• dc.contributor.author Suárez-Calvet, Marc
• dc.contributor.author Gispert López, Juan Domingo
• dc.date.accessioned 2025-10-03T06:20:51Z
• dc.date.available 2025-10-03T06:20:51Z
• dc.date.issued 2024
• dc.description.abstract Introduction: Cerebral blood flow (CBF) is reduced in cognitively impaired (CI) Alzheimer's disease (AD) patients. We checked the sensitivity of time-encoded arterial spin labeling (te-ASL) in measuring CBF alterations in individuals with positive AD biomarkers and associations with relevant biomarkers in cognitively unimpaired (CU) individuals. Methods: We compared te-ASL with single-postlabel delay (PLD) ASL in measuring CBF in 59 adults across the AD continuum, classified as CU amyloid beta (Aβ) negative (-), CU Aβ positive (+), and CI Aβ+. We sought associations of CBF with biomarkers of AD, cerebrovascular disease, synaptic dysfunction, neurodegeneration, and cognition in CU participants. Results: te-ASL was more sensitive at detecting CBF reduction in the CU Aβ+ and CI Aβ+ groups. In CU participants, lower CBF was associated with altered biomarkers of Aβ, tau, synaptic dysfunction, and neurodegeneration. Discussion: CBF reduction occurs early in the AD continuum. te-ASL is more sensitive than single-PLD ASL at detecting CBF changes in AD. Highlights: Lower CBF can be detected in CU subjects in the early AD continuum. te-ASL is more sensitive than single-PLD ASL at detecting CBF alterations in AD. CBF is linked to biomarkers of AD, synaptic dysfunction, and neurodegeneration.
• dc.description.sponsorship We want to express our most sincere gratitude to the ALFA project participants and relatives, without whom this research would not have been possible. We thank Roche Diagnostics International Ltd for providing the NeuroToolKit kits to measure CSF biomarkers, Eli Lilly and Company for providing the measurements of the in-house assay for CSF and plasma p-tau217, and GE Healthcare for providing the doses of [18F] flutemetamol PET. Lastly, we would like to thank Valeria Di Giacomo, PhD, and Allison Clark, from ThePaperMill, for providing writing support, funded by The Fundació Pasqual Maragall. Marc Suárez-Calvet receives funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant agreement No. 948677), the Instituto de Salud Carlos III (ISCIII) through projects PI19/00155 and PI22/00456 (cofunded by the European Union FEDER), the Department of Research and Universities of the Generalitat de Catalunya through the project 2021 SGR 01137, the HNA Foundation through the project PROAD, and the ERA PerMed ERA-NET and the Department of Health of the Generalitat de Catalunya (DS-CAT) through the project SLD077/21/000001. Moreover, Marc receives support from a fellowship provided by “la Caixa” Foundation (ID 100010434) and from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant agreement No. 847648 (fellowship code LCF/BQ/PR21/11840004). Henrik Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (Nos. 2022-01018 and 2019-02397), the European Union's Horizon Europe research and innovation program under Grant agreement No. 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (No. 201809-2016862), the AD Strategic Fund and the Alzheimer's Association (Nos. ADSF-21-831376-C, ADSF-21-831381-C, and ADSF-21-831377-C), the Bluefield Project, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (FO2022-0270), the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant agreement No. 860197 (MIRIADE), the European Union Joint Programme—Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI-1003). Oriol Grau-Rivera receives funding from the Alzheimer's Association Research Fellowship Program (2019-AARF-644568), the Instituto de Salud Carlos III (ISCIII) through the project PI19/00117 (cofunded by the European Unior FEDER), and the MCIN/AEI/10.13039/501100011033 through the project IJC2020-043417-I (cofunded by the European Union NextGenerationEU/PRTR).
• dc.format.mimetype application/pdf
• dc.identifier.citation Falcon C, Montesinos P, Václavů L, Kassinopoulos M, Minguillon C, Fauria K, et al. Time-encoded ASL reveals lower cerebral blood flow in the early AD continuum. Alzheimers Dement. 2024 Aug;20(8):5183-97. DOI: 10.1002/alz.14059
• dc.identifier.doi http://dx.doi.org/10.1002/alz.14059
• dc.identifier.issn 1552-5260
• dc.identifier.uri http://hdl.handle.net/10230/71351
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Alzheimers Dement. 2024 Aug;20(8):5183-97
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/948677
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/847648
• dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101053962
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/860197
• dc.rights © 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Alzheimer's disease
• dc.subject.keyword Amyloid beta
• dc.subject.keyword Magnetic resonance imaging
• dc.subject.keyword Neurodegeneration
• dc.subject.keyword Neurofilament light
• dc.subject.keyword p‐tau
• dc.subject.keyword Single‐postlabel delay arterial spin labeling
• dc.subject.keyword Synaptic dysfunction
• dc.subject.keyword Tau proteins
• dc.title Time-encoded ASL reveals lower cerebral blood flow in the early AD continuum
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion