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Differential associ...
Differential associations of APOE-epsilon 2 and APOE-epsilon 4 alleles with PET-measured amyloid-beta and tau deposition in older individuals without dementia
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Salvado, G. (author)
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- Grothe, Michel J., 1981 (author)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Groot, C. (author)
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- Rial, Alexis Moscoso (author)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Schöll, Michael, 1980 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Wallenberg Centre for Molecular and Translational Medicine,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
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Gispert, J. D. (author)
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Ossenkoppele, R. (author)
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(creator_code:org_t)
- 2021-02-01
- 2021
- English.
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 48, s. 2212-2224
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Abstract
Subject headings
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- Purpose To examine associations between the APOE-epsilon 2 and APOE-epsilon 4 alleles and core Alzheimer's disease (AD) pathological hallmarks as measured by amyloid-beta (A beta) and tau PET in older individuals without dementia. Methods We analyzed data from 462 ADNI participants without dementia who underwent A beta ([F-18]florbetapir or [F-18]florbetaben) and tau ([F-18]flortaucipir) PET, structural MRI, and cognitive testing. Employing APOE-epsilon 3 homozygotes as the reference group, associations between APOE-epsilon 2 and APOE-epsilon 4 carriership with global A beta 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 A beta mediated the cross-sectional and longitudinal associations between APOE genotype and tau. Results Compared to APOE-epsilon 3 homozygotes, APOE-epsilon 2 carriers had lower global A beta burden (beta(std) [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-epsilon 4 participants showed higher A beta (beta(std) [95%CI]: 0.64 [0.42, 0.82], p < 0.001) and tau burden (beta(std) range: 0.27-0.51, all p < 0.006). In mediation analyses, APOE-epsilon 4 only retained an A beta-independent effect on tau in the ERC. APOE-epsilon 4 showed a trend towards increased tau accumulation over time in Braak-V/VI compared to APOE-epsilon 3 homozygotes (beta(std) [95%CI]: 0.10 [- 0.02, 0.18], p = 0.11), and this association was fully mediated by baseline A beta. Conclusion Our data suggest that the established protective effect of the APOE-epsilon 2 allele against developing clinical AD is primarily linked to resistance against A beta deposition rather than tau pathology.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- Tau
- Amyloid-beta
- Cross-sectional
- Longitudinal
- Sex interaction
- Cognition
- Hippocampal volumes
- APOE
- PET
- Radiology
- Nuclear Medicine & Medical Imaging
Publication and Content Type
- ref (subject category)
- art (subject category)
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