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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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- Medientyp: E-Artikel
- Titel: KL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer’s disease
- Beteiligte: 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; [...]
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Erschienen:
Springer Science and Business Media LLC, 2021
- Erschienen in: Nature Communications, 12 (2021) 1
- Sprache: Englisch
- DOI: 10.1038/s41467-021-23755-z
- ISSN: 2041-1723
- Entstehung:
- Anmerkungen:
- Beschreibung: <jats:title>Abstract</jats:title><jats:p>Klotho-VS heterozygosity (KL-VS<jats:sup>het</jats:sup>) is associated with reduced risk of Alzheimer’s disease (AD). However, whether KL-VS<jats:sup>het</jats: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<jats:sup>het</jats: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<jats:sup>het</jats: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<jats:sup>het</jats:sup>on tau-PET was stronger in Klotho mRNA-expressing brain regions mapped onto a gene expression atlas. KL-VS<jats:sup>het</jats: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<jats:sup>het</jats:sup>carriers versus non-carriers. Together, our findings provide evidence to suggest a protective role of KL-VS<jats:sup>het</jats:sup>against amyloid-related tau pathology and tau-related memory impairments in elderly humans at risk of AD dementia.</jats:p>
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