Differential associations of APOE-ε2 and APOE-ε4 alleles with PET-measured amyloid-β and tau deposition in older individuals without dementia
(2021) In European Journal of Nuclear Medicine and Molecular Imaging 48(7). p.2212-2224- 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.... (More)
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.
(Less)
- author
- Salvadó, Gemma ; Grothe, Michel J. ; Groot, Colin ; Moscoso, Alexis ; Schöll, Michael LU ; Gispert, Juan Domingo and Ossenkoppele, Rik LU
- organization
- publishing date
- 2021-07-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Amyloid-β, APOE, Cognition, Cross-sectional, Hippocampal volumes, Longitudinal, PET, Sex interaction, Tau
- in
- European Journal of Nuclear Medicine and Molecular Imaging
- volume
- 48
- issue
- 7
- pages
- 13 pages
- publisher
- Springer
- external identifiers
-
- pmid:33521872
- scopus:85100014160
- ISSN
- 1619-7070
- DOI
- 10.1007/s00259-021-05192-8
- language
- English
- LU publication?
- yes
- id
- 850af862-e059-4ca3-aa14-6138d503e48f
- date added to LUP
- 2021-02-10 09:02:30
- date last changed
- 2024-09-19 16:10:31
@article{850af862-e059-4ca3-aa14-6138d503e48f, abstract = {{<p>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 ([<sup>18</sup>F]florbetapir or [<sup>18</sup>F]florbetaben) and tau ([<sup>18</sup>F]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 (β<sub>std</sub> [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 (β<sub>std</sub> [95%CI]: 0.64 [0.42, 0.82], p < 0.001) and tau burden (β<sub>std</sub> 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 (β<sub>std</sub> [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.</p>}}, author = {{Salvadó, Gemma and Grothe, Michel J. and Groot, Colin and Moscoso, Alexis and Schöll, Michael and Gispert, Juan Domingo and Ossenkoppele, Rik}}, issn = {{1619-7070}}, keywords = {{Amyloid-β; APOE; Cognition; Cross-sectional; Hippocampal volumes; Longitudinal; PET; Sex interaction; Tau}}, language = {{eng}}, month = {{07}}, number = {{7}}, pages = {{2212--2224}}, publisher = {{Springer}}, series = {{European Journal of Nuclear Medicine and Molecular Imaging}}, title = {{Differential associations of APOE-ε2 and APOE-ε4 alleles with PET-measured amyloid-β and tau deposition in older individuals without dementia}}, url = {{http://dx.doi.org/10.1007/s00259-021-05192-8}}, doi = {{10.1007/s00259-021-05192-8}}, volume = {{48}}, year = {{2021}}, }