2021-06-22
KL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer’s disease
Publication
Publication
Nature Communications , Volume 12 - Issue 1
<p>Klotho-VS heterozygosity (KL-VS<sup>het</sup>) is associated with reduced risk of Alzheimer’s disease (AD). However, whether KL-VS<sup>het</sup> 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<sup>het</sup> 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<sup>het</sup> 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<sup>het</sup> on tau-PET was stronger in Klotho mRNA-expressing brain regions mapped onto a gene expression atlas. KL-VS<sup>het</sup> 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<sup>het</sup> carriers versus non-carriers. Together, our findings provide evidence to suggest a protective role of KL-VS<sup>het</sup> against amyloid-related tau pathology and tau-related memory impairments in elderly humans at risk of AD dementia.</p>
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| doi.org/10.1038/s41467-021-23755-z, hdl.handle.net/1765/136135 | |
| Nature Communications | |
| Organisation | Erasmus MC: University Medical Center Rotterdam |
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the Alzheimer's Disease Neuroimaging Initiative, J. (Julia) Neitzel, Nicolai Franzmeier, Anna Rubinski, Martin Dichgans, Matthias Brendel, … L.S. (Li Shen) Ho. (2021). KL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer’s disease. Nature Communications, 12(1). doi:10.1038/s41467-021-23755-z |
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