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

Kód výsledku v 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>

Nalezeny alternativní kódy

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

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

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

Journal of Alzheimers Disease

ISSN

1387-2877

e-ISSN

—

Svazek periodika

105

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

13

Strana od-do

159-171

Kód UT WoS článku

001459090100001

EID výsledku v databázi Scopus

2-s2.0-105004756509