TY  - JOUR
ID  - discovery10131324
KW  - Alzheimer's disease
KW  -  Dementia
KW  -  Haplotypes
KW  -  Molecular imaging
IS  - 1
A1  - Neitzel, J
A1  - Franzmeier, N
A1  - Rubinski, A
A1  - Dichgans, M
A1  - Brendel, M
A1  - Alzheimer?s Disease Neuroimaging Initiative (ADNI), .
A1  - Malik, R
A1  - Ewers, M
VL  - 12
UR  - https://doi.org/10.1038/s41467-021-23755-z
AV  - public
JF  - Nature Communications
N2  - 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.
TI  - KL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer's disease
Y1  - 2021///
N1  - © 2021 Springer Nature Limited. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
ER  -