ORCID: https://orcid.org/0000-0002-0654-387X; Brendel, Matthias
ORCID: https://orcid.org/0000-0002-9247-2843; Malik, Rainer and Ewers, Michael
(2021):
KL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer's disease.
In: Nature Communications, Vol. 12, No. 1, 3825
[PDF, 1MB]
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.
Item Type: | Journal article |
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Faculties: | Medicine > Munich Cluster for Systems Neurology (SyNergy) Medicine > Institute for Stroke and Dementia Research (ISD) |
Subjects: | 600 Technology > 610 Medicine and health |
URN: | urn:nbn:de:bvb:19-epub-90797-4 |
Language: | English |
Item ID: | 90797 |
Date Deposited: | 02. Feb 2022, 09:18 |
Last Modified: | 06. Jun 2024, 15:16 |
DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |