KLOTHO-VS heterozygosity, α-klotho protein levels and cognitive performance in Alzheimer's disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023884%3A_____%2F25%3A00010186" target="_blank" >RIV/00023884:_____/25:00010186 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/25:10504784 RIV/00064203:_____/25:10504784

Výsledek na webu

<a href="https://link.springer.com/article/10.1186/s13195-025-01878-5?utm_source=getftr&utm_medium=getftr&utm_campaign=getftr_pilot&getft_integrator=clarivate" target="_blank" >https://link.springer.com/article/10.1186/s13195-025-01878-5?utm_source=getftr&utm_medium=getftr&utm_campaign=getftr_pilot&getft_integrator=clarivate</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s13195-025-01878-5" target="_blank" >10.1186/s13195-025-01878-5</a>

Jazyk výsledku

angličtina

Název v původním jazyce

KLOTHO-VS heterozygosity, α-klotho protein levels and cognitive performance in Alzheimer's disease

Popis výsledku v původním jazyce

KLOTHO-VS (KL-VS) heterozygosity, a variant of the KLOTHO gene, and its encoded protein, alpha-Klotho, are associated with brain health and show neuroprotective potential against Alzheimer's disease (AD). We aimed to assess whether KL-VS heterozygosity, cerebrospinal fluid (CSF) and serum soluble alpha-Klotho (s alpha Kl) levels, would be associated with a lower likelihood of AD and better performance on memory and other cognitive domains in individuals with AD dementia, amnestic mild cognitive impairment (aMCI) due to AD, and cognitively unimpaired controls.MethodsIn this cross-sectional study, we analyzed two partially overlapping subsamples derived from 296 participants from the Czech Brain Aging Study. The first subsample included 196 participants with KL-VS haplotype data: 71 with AD dementia, 84 with aMCI due to AD, and 41 cognitively unimpaired controls. The second subsample included 147 participants with CSF and/or serum s alpha Kl measurements, including 58 with AD dementia, 59 with aMCI due to AD, and 30 cognitively unimpaired controls. Diagnoses of aMCI and AD dementia were confirmed by positive CSF biomarkers and/or amyloid PET imaging. Logistic regression assessed how KL-VS heterozygosity influenced the odds of aMCI or dementia due to AD. Linear regression investigated associations between cognitive performance and either KL-VS heterozygosity or CSF/serum s alpha Kl levels. Analysis of variance and analysis of covariance with post-hoc tests were used to compare s alpha Kl levels across study groups.ResultsKL-VS heterozygosity carriers showed a consistent trend towards lower odds of being classified with aMCI and dementia due to AD, with similar patterns in both Apolipoprotein E epsilon 4 (APOE epsilon 4) allele carriers and non-carriers, although none of the associations reached statistical significance despite moderate (rather than small) effect sizes. Among individuals with aMCI due to AD, KL-VS heterozygotes displayed better memory performance (beta = 0.61, p = .008), particularly those who also carried the APOE epsilon 4 allele (beta = 0.64, p = .042). Results with other cognitive domains were non-significant. No significant differences in s alpha Kl levels were found between study groups, and soluble alpha-Klotho levels did not associate with memory performance.ConclusionsKL-VS heterozygosity may be linked to lower likelihood of classification as aMCI or dementia due to AD, and its association with memory might be specific to the aMCI stage of AD and modulated by APOE epsilon 4 status.

Název v anglickém jazyce

KLOTHO-VS heterozygosity, α-klotho protein levels and cognitive performance in Alzheimer's disease

Popis výsledku anglicky

KLOTHO-VS (KL-VS) heterozygosity, a variant of the KLOTHO gene, and its encoded protein, alpha-Klotho, are associated with brain health and show neuroprotective potential against Alzheimer's disease (AD). We aimed to assess whether KL-VS heterozygosity, cerebrospinal fluid (CSF) and serum soluble alpha-Klotho (s alpha Kl) levels, would be associated with a lower likelihood of AD and better performance on memory and other cognitive domains in individuals with AD dementia, amnestic mild cognitive impairment (aMCI) due to AD, and cognitively unimpaired controls.MethodsIn this cross-sectional study, we analyzed two partially overlapping subsamples derived from 296 participants from the Czech Brain Aging Study. The first subsample included 196 participants with KL-VS haplotype data: 71 with AD dementia, 84 with aMCI due to AD, and 41 cognitively unimpaired controls. The second subsample included 147 participants with CSF and/or serum s alpha Kl measurements, including 58 with AD dementia, 59 with aMCI due to AD, and 30 cognitively unimpaired controls. Diagnoses of aMCI and AD dementia were confirmed by positive CSF biomarkers and/or amyloid PET imaging. Logistic regression assessed how KL-VS heterozygosity influenced the odds of aMCI or dementia due to AD. Linear regression investigated associations between cognitive performance and either KL-VS heterozygosity or CSF/serum s alpha Kl levels. Analysis of variance and analysis of covariance with post-hoc tests were used to compare s alpha Kl levels across study groups.ResultsKL-VS heterozygosity carriers showed a consistent trend towards lower odds of being classified with aMCI and dementia due to AD, with similar patterns in both Apolipoprotein E epsilon 4 (APOE epsilon 4) allele carriers and non-carriers, although none of the associations reached statistical significance despite moderate (rather than small) effect sizes. Among individuals with aMCI due to AD, KL-VS heterozygotes displayed better memory performance (beta = 0.61, p = .008), particularly those who also carried the APOE epsilon 4 allele (beta = 0.64, p = .042). Results with other cognitive domains were non-significant. No significant differences in s alpha Kl levels were found between study groups, and soluble alpha-Klotho levels did not associate with memory performance.ConclusionsKL-VS heterozygosity may be linked to lower likelihood of classification as aMCI or dementia due to AD, and its association with memory might be specific to the aMCI stage of AD and modulated by APOE epsilon 4 status.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/LX22NPO5107" target="_blank" >LX22NPO5107: Národní ústav pro neurologický výzkum</a><br>

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Alzheimers Research & Therapy

ISSN

1758-9193

e-ISSN

—

Svazek periodika

17

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

—

Kód UT WoS článku

001603599200001

EID výsledku v databázi Scopus

2-s2.0-105020312092