期刊
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
卷 48, 期 7, 页码 2212-2224出版社
SPRINGER
DOI: 10.1007/s00259-021-05192-8
关键词
Tau; Amyloid-beta; Cross-sectional; Longitudinal; Sex interaction; Cognition; Hippocampal volumes; APOE; PET
资金
- Alzheimer Nederland
- Miguel Servet program of the Spanish Instituto de Salud Carlos III (ISCIII-FEDER) [CP19/00031]
- Spanish Ministry of Science and Innovation [RYC-2013-13054]
- Knut and Alice Wallenberg Foundation (Wallenberg Centre for Molecular and Translational Medicine) [KAW 2014.0363]
- Swedish Research Council [2017-02869]
- Swedish government [ALFGBG-813971]
- Swedish Alzheimer Foundation [AF740191]
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Cogstate
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. HoffmannLa Roche Ltd.
- Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Lumosity
- Lundbeck
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
The study found that APOE-ε2 carriers had lower Aβ deposition compared to APOE-ε3 homozygotes, while APOE-ε4 carriers showed significantly increased Aβ and tau deposition.
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.
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