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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; 6/22/2021, Vol. 12 Issue 1, p1-12, 12p
- Publication Year :
- 2021
-
Abstract
- Klotho-VS heterozygosity (KL-VS<superscript>het</superscript>) is associated with reduced risk of Alzheimer's disease (AD). However, whether KL-VS<superscript>het</superscript> 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-VS<superscript>het</superscript> 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-VS<superscript>het</superscript> 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-VS<superscript>het</superscript> on tau-PET was stronger in Klotho mRNA-expressing brain regions mapped onto a gene expression atlas. KL-VS<superscript>het</superscript> 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-VS<superscript>het</superscript> carriers versus non-carriers. Together, our findings provide evidence to suggest a protective role of KL-VS<superscript>het</superscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 12
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 151025861
- Full Text :
- https://doi.org/10.1038/s41467-021-23755-z