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KL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer’s disease
- Source :
- Nature Communications, 12(1):3825. Nature Publishing Group, Nature Communications, Nature Communications 12(1), 3825 (2021). doi:10.1038/s41467-021-23755-z
- Publication Year :
- 2021
-
Abstract
- 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.<br />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.
- Subjects :
- Male
Heterozygote
metabolism [Amyloid beta-Peptides]
Molecular imaging
Gene Expression
genetics [Alzheimer Disease]
klotho protein
tau Proteins
Polymorphism, Single Nucleotide
Article
metabolism [Apolipoproteins E]
Apolipoproteins E
genetics [Memory Disorders]
Alzheimer Disease
mental disorders
Humans
metabolism [Glucuronidase]
diagnostic imaging [Brain]
Klotho Proteins
Aged
Glucuronidase
Memory Disorders
Amyloid beta-Peptides
genetics [Glucuronidase]
methods [Positron-Emission Tomography]
metabolism [Memory Disorders]
Brain
Alzheimer's disease
Middle Aged
metabolism [tau Proteins]
Haplotypes
metabolism [Brain]
Positron-Emission Tomography
genetics [Apolipoproteins E]
Dementia
Female
ddc:500
metabolism [Alzheimer Disease]
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications, 12(1):3825. Nature Publishing Group, Nature Communications, Nature Communications 12(1), 3825 (2021). doi:10.1038/s41467-021-23755-z
- Accession number :
- edsair.pmid.dedup....ba889c74202405fa0432553523acbc1d