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Neitzel, Julia; Franzmeier, Nicolai; Rubinski, Anna; Dichgans, Martin; Brendel, Matthias; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Liu, Enchi; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; [...]

KL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer’s disease

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  • Media type: E-Article
  • Title: KL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer’s disease
  • Contributor: Neitzel, Julia; Franzmeier, Nicolai; Rubinski, Anna; Dichgans, Martin; Brendel, Matthias; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Liu, Enchi; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; [...]
  • Published: Springer Science and Business Media LLC, 2021
  • Published in: Nature Communications, 12 (2021) 1
  • Language: English
  • DOI: 10.1038/s41467-021-23755-z
  • ISSN: 2041-1723
  • Origination:
  • Footnote:
  • Description: AbstractKlotho-VS heterozygosity (KL-VShet) is associated with reduced risk of Alzheimer’s disease (AD). However, whether KL-VShetis 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-VShetand 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-VShetshowed 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-VSheton tau-PET was stronger in Klotho mRNA-expressing brain regions mapped onto a gene expression atlas. KL-VShetwas 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-VShetcarriers versus non-carriers. Together, our findings provide evidence to suggest a protective role of KL-VShetagainst amyloid-related tau pathology and tau-related memory impairments in elderly humans at risk of AD dementia.
  • Access State: Open Access