期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-23755-z
关键词
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资金
- DAAD
- Alzheimer Forschung Initiative (AFI) [15035]
- Legerlotz Stiftung
- LMUexcellent
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) grant for major research instrumentation (DFG) [INST 409/193-1 FUGG]
- Hertie Foundation for Clinical Neurosciences
- European Union [666881, 667375]
- DFG as part of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy) [390857198, CRC 1123]
- 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
- 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. Hoffmann-La 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
- AbbVie
- LMU Forderung Forschung Lehre [1032]
- MRC [UKDRI-1001] Funding Source: UKRI
The Klotho-VS haplotype is associated with reduced risk of Alzheimer's disease and dementia. This study demonstrates an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data. KL-VShet carriers show lower levels of tau-PET per unit increase in amyloid-PET, suggesting a protective role against amyloid-related tau pathology and memory impairments in elderly individuals at risk of AD dementia.
Klotho-VS heterozygosity (KL-VShet) is associated with reduced risk of Alzheimer's disease (AD). However, whether KL-VShet is associated with lower levels of pathologic tau, i.e., the key AD pathology driving neurodegeneration and cognitive decline, is unknown. Here, we assessed the interaction between KL-VShet and levels of beta-amyloid, a key driver of tau pathology, on the levels of PET-assessed neurofibrillary tau in 551 controls and patients across the AD continuum. KL-VShet showed lower cross-sectional and longitudinal increase in tau-PET per unit increase in amyloid-PET when compared to that of non-carriers. This association of KL-VShet on tau-PET was stronger in Klotho mRNA-expressing brain regions mapped onto a gene expression atlas. KL-VShet was related to better memory functions in amyloid-positive participants and this association was mediated by lower tau-PET. Amyloid-PET levels did not differ between KL-VShet carriers versus non-carriers. Together, our findings provide evidence to suggest a protective role of KL-VShet against amyloid-related tau pathology and tau-related memory impairments in elderly humans at risk of AD dementia. The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer's disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.
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