In:
Nature Communications, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2021-06-22)
Abstract:
Klotho-VS heterozygosity (KL-VS het ) is associated with reduced risk of Alzheimer’s disease (AD). However, whether KL-VS het 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 het 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 het 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 het on tau-PET was stronger in Klotho mRNA-expressing brain regions mapped onto a gene expression atlas. KL-VS het 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 het carriers versus non-carriers. Together, our findings provide evidence to suggest a protective role of KL-VS het against amyloid-related tau pathology and tau-related memory impairments in elderly humans at risk of AD dementia.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-021-23755-z
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2553671-0