Association between polygenic risk score of Alzheimer's disease and plasma phosphorylated tau in individuals from the Alzheimer's disease neuroimaging initiative

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  • dc.contributor.author Zettergren, Anna
  • dc.contributor.author Lord, Jodie
  • dc.contributor.author Ashton, Nicholas J.
  • dc.contributor.author Benedet, Andrea L.
  • dc.contributor.author Karikari, Thomas K.
  • dc.contributor.author Lantero Rodriguez, Juan
  • dc.contributor.author Alzheimer’s Disease Neuroimaging Initiative
  • dc.contributor.author Snellman, Anniina
  • dc.contributor.author Suárez-Calvet, Marc
  • dc.contributor.author Proitsi, Petroula
  • dc.contributor.author Zetterberg, Henrik
  • dc.contributor.author Blennow, Kaj
  • dc.date.accessioned 2021-05-18T07:00:23Z
  • dc.date.available 2021-05-18T07:00:23Z
  • dc.date.issued 2021
  • dc.description.abstract Background: Recent studies suggest that plasma phosphorylated tau181 (p-tau181) is a highly specific biomarker for Alzheimer's disease (AD)-related tau pathology. It has great potential for the diagnostic and prognostic evaluation of AD, since it identifies AD with the same accuracy as tau PET and CSF p-tau181 and predicts the development of AD dementia in cognitively unimpaired (CU) individuals and in those with mild cognitive impairment (MCI). Plasma p-tau181 may also be used as a biomarker in studies exploring disease pathogenesis, such as genetic or environmental risk factors for AD-type tau pathology. The aim of the present study was to investigate the relation between polygenic risk scores (PRSs) for AD and plasma p-tau181. Methods: Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) was used to examine the relation between AD PRSs, constructed based on findings in recent genome-wide association studies, and plasma p-tau181, using linear regression models. Analyses were performed in the total sample (n = 818), after stratification on diagnostic status (CU (n = 236), MCI (n = 434), AD dementia (n = 148)), and after stratification on Aβ pathology status (Aβ positives (n = 322), Aβ negatives (n = 409)). Results: Associations between plasma p-tau181 and APOE PRSs (p = 3e-18-7e-15) and non-APOE PRSs (p = 3e-4-0.03) were seen in the total sample. The APOE PRSs were associated with plasma p-tau181 in all diagnostic groups (CU, MCI, and AD dementia), while the non-APOE PRSs were associated only in the MCI group. The APOE PRSs showed similar results in amyloid-β (Aβ)-positive and negative individuals (p = 5e-5-1e-3), while the non-APOE PRSs were associated with plasma p-tau181 in Aβ positives only (p = 0.02). Conclusions: Polygenic risk for AD including APOE was found to associate with plasma p-tau181 independent of diagnostic and Aβ pathology status, while polygenic risk for AD beyond APOE was associated with plasma p-tau181 only in MCI and Aβ-positive individuals. These results extend the knowledge about the relation between genetic risk for AD and p-tau181, and further support the usefulness of plasma p-tau181 as a biomarker of AD.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Zettergren A, Lord J, Ashton NJ, Benedet AL, Karikari TK, Lantero Rodriguez J, et al. Association between polygenic risk score of Alzheimer's disease and plasma phosphorylated tau in individuals from the Alzheimer's disease neuroimaging initiative. Alzheimers Res Ther. 2021 Jan 8; 13(1): 17. DOI: 10.1186/s13195-020-00754-8
  • dc.identifier.doi http://dx.doi.org/10.1186/s13195-020-00754-8
  • dc.identifier.issn 1758-9193
  • dc.identifier.uri http://hdl.handle.net/10230/47575
  • dc.language.iso eng
  • dc.publisher BioMed Central
  • dc.rights Copyright © The Author(s) 2021. Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to th
  • 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 Plasma phosphorylated tau 181
  • dc.subject.keyword Polygenic risk score
  • dc.title Association between polygenic risk score of Alzheimer's disease and plasma phosphorylated tau in individuals from the Alzheimer's disease neuroimaging initiative
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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