Associations of KLOTHO-VS heterozygosity and α-Klotho protein with cerebrospinal fluid Alzheimer's disease biomarkers

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023884%3A_____%2F25%3A00010194" target="_blank" >RIV/00023884:_____/25:00010194 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/25:10496393 RIV/00064203:_____/25:10496393

Result on the web

<a href="https://journals.sagepub.com/doi/10.1177/13872877251326199?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed" target="_blank" >https://journals.sagepub.com/doi/10.1177/13872877251326199?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1177/13872877251326199" target="_blank" >10.1177/13872877251326199</a>

Result language

angličtina

Original language name

Associations of KLOTHO-VS heterozygosity and α-Klotho protein with cerebrospinal fluid Alzheimer's disease biomarkers

Original language description

Background KLOTHO-VS heterozygosity (KL-VSHET) and soluble alpha-Klotho (s alpha Kl) protein interfere with Alzheimer's disease (AD) pathophysiology, but the specific relationships remain unclear. This study explored these associations across the AD continuum, focusing on core AD biomarkers and markers of neurodegeneration, neuroinflammation, and synaptic dysfunction. Objective We investigated whether 1) KL-VSHET is associated with lower AD biomarker burden (A beta(42), A beta(42/40) ratio, P-tau181, T-tau) and neurodegeneration (NfL); 2) s alpha Kl relates to AD biomarkers, neurodegeneration (NfL), neuroinflammation (GFAP), and synaptic dysfunction (Ng); 3) associations vary by APOE epsilon 4 status and clinical subgroup. Methods Participants (n = 223) were categorized as cognitively healthy (n = 38), aMCI-AD (n = 94), and AD dementia (n = 91). KLOTHO genotyping was available for 128 participants; 138 had cerebrospinal fluid (CSF) and serum s alpha Kl measurements; and 42 had both. Multiple linear regression evaluated associations between KL-VSHET, s alpha Kl levels, and biomarkers, stratified by APOE epsilon 4 status and clinical subgroup. Results Overall, the associations between KL-VSHET and higher CSF A beta(42) and A beta(42/40) ratio were non-significant (ps >= 0.059) except when restricted to APOE epsilon 4 carriers only (beta = 0.11, p = 0.008 and beta = 0.16, p = 0.033, respectively). Within clinical subgroups, KL-VSHET was positively associated with A beta(42/40) ratio only in aMCI-AD (beta = 0.23, p = 0.034). No significant associations were observed between KL-VSHET and tau biomarkers or NfL. For s alpha Kl, associations with biomarkers were non-significant except for a negative association of serum s alpha Kl with P-tau181 in aMCI-AD (beta = -0.25, p = 0.036) and a positive association with A beta(42/40) ratio in APOE epsilon 4 non-carriers (beta = 0.24 p = 0.047). Conclusions KL-VSHET may help protect against amyloid pathology, particularly in the presence of APOE epsilon 4, and regardless of APOE status in aMCI-AD.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

<a href="/en/project/LX22NPO5107" target="_blank" >LX22NPO5107: National institute for Neurological Research</a><br>

Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2025

Confidentiality

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

Name of the periodical

Journal of Alzheimers Disease

ISSN

1387-2877

e-ISSN

—

Volume of the periodical

105

Issue of the periodical within the volume

1

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

13

Pages from-to

159-171

UT code for WoS article

001459090100001

EID of the result in the Scopus database

2-s2.0-105004756509