Differential associations of APOE-ε2 and APOE-ε4 alleles with PET-measured amyloid-β and tau deposition in older individuals without dementia

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• dc.contributor.author Salvadó, Gemma
• dc.contributor.author Grothe, Michel J.
• dc.contributor.author Groot, Colin
• dc.contributor.author Moscoso, Alexis
• dc.contributor.author Schöll, Michael
• dc.contributor.author Gispert López, Juan Domingo
• dc.contributor.author Ossenkoppele, Rik
• dc.contributor.author Alzheimer’s Disease Neuroimaging Initiative
• dc.date.accessioned 2021-04-30T07:33:44Z
• dc.date.available 2021-04-30T07:33:44Z
• dc.date.issued 2021
• dc.description.abstract Purpose: To examine associations between the APOE-ε2 and APOE-ε4 alleles and core Alzheimer's disease (AD) pathological hallmarks as measured by amyloid-β (Aβ) and tau PET in older individuals without dementia. Methods: We analyzed data from 462 ADNI participants without dementia who underwent Aβ ([18F]florbetapir or [18F]florbetaben) and tau ([18F]flortaucipir) PET, structural MRI, and cognitive testing. Employing APOE-ε3 homozygotes as the reference group, associations between APOE-ε2 and APOE-ε4 carriership with global Aβ PET and regional tau PET measures (entorhinal cortex (ERC), inferior temporal cortex, and Braak-V/VI neocortical composite regions) were investigated using linear regression models. In a subset of 156 participants, we also investigated associations between APOE genotype and regional tau accumulation over time using linear mixed models. Finally, we assessed whether Aβ mediated the cross-sectional and longitudinal associations between APOE genotype and tau. Results: Compared to APOE-ε3 homozygotes, APOE-ε2 carriers had lower global Aβ burden (βstd [95% confidence interval (CI)]: - 0.31 [- 0.45, - 0.16], p = 0.034) but did not differ on regional tau burden or tau accumulation over time. APOE-ε4 participants showed higher Aβ (βstd [95%CI]: 0.64 [0.42, 0.82], p < 0.001) and tau burden (βstd range: 0.27-0.51, all p < 0.006). In mediation analyses, APOE-ε4 only retained an Aβ-independent effect on tau in the ERC. APOE-ε4 showed a trend towards increased tau accumulation over time in Braak-V/VI compared to APOE-ε3 homozygotes (βstd [95%CI]: 0.10 [- 0.02, 0.18], p = 0.11), and this association was fully mediated by baseline Aβ. Conclusion: Our data suggest that the established protective effect of the APOE-ε2 allele against developing clinical AD is primarily linked to resistance against Aβ deposition rather than tau pathology.
• dc.format.mimetype application/pdf
• dc.identifier.citation Salvadó G, Grothe MJ, Groot C, Moscoso A, Schöll M, Gispert JD, Ossenkoppele R; Alzheimer’s Disease Neuroimaging Initiative. Differential associations of APOE-ε2 and APOE-ε4 alleles with PET-measured amyloid-β and tau deposition in older individuals without dementia. Eur J Nucl Med Mol Imaging. 2021;48(7):2212-24. DOI: 10.1007/s00259-021-05192-8
• dc.identifier.doi http://dx.doi.org/10.1007/s00259-021-05192-8
• dc.identifier.issn 1619-7070
• dc.identifier.uri http://hdl.handle.net/10230/47264
• dc.language.iso eng
• dc.publisher Springer
• dc.relation.ispartof Eur J Nucl Med Mol Imaging. 2021;48(7):2212-24
• dc.rights © The Author(s) 2021. Open Access This 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/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword APOE
• dc.subject.keyword Amyloid-β
• dc.subject.keyword Cognition
• dc.subject.keyword Cross-sectional
• dc.subject.keyword Hippocampal volumes
• dc.subject.keyword Longitudinal
• dc.subject.keyword PET
• dc.subject.keyword Sex interaction
• dc.subject.keyword Tau
• dc.title Differential associations of APOE-ε2 and APOE-ε4 alleles with PET-measured amyloid-β and tau deposition in older individuals without dementia
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion