Associations of KLOTHO-VS heterozygosity and α-Klotho protein with cerebrospinal fluid Alzheimer's disease biomarkers
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View abstract on PubMed
Summary
This summary is machine-generated.KLOTHO-VS heterozygosity may protect against Alzheimer's amyloid pathology, especially in APOE ε4 carriers and individuals with mild cognitive impairment. Soluble α-Klotho shows varied associations with AD biomarkers.
Area Of Science
- Neuroscience
- Genetics
- Biochemistry
Background
- Soluble α-Klotho (sαKl) and KLOTHO-VS heterozygosity (KL-VSHET) are implicated in Alzheimer's disease (AD) pathophysiology.
- Their specific roles across the AD continuum and in relation to core AD biomarkers, neurodegeneration, neuroinflammation, and synaptic dysfunction require clarification.
Purpose Of The Study
- To investigate the association of KL-VSHET with AD biomarker burden (Aβ42, Aβ42/40, P-tau181, T-tau) and neurodegeneration (NfL).
- To examine the relationship between sαKl levels and AD biomarkers, neurodegeneration (NfL), neuroinflammation (GFAP), and synaptic dysfunction (Ng).
- To determine if these associations differ based on APOE ε4 status and clinical AD subgroup.
Main Methods
- Cross-sectional study of 223 participants: cognitively healthy, mild cognitive impairment due to AD (aMCI-AD), and AD dementia.
- KLOTHO genotyping and measurement of cerebrospinal fluid (CSF) and serum sαKl.
- Multiple linear regression analyses stratified by APOE ε4 status and clinical subgroup.
Main Results
- KL-VSHET showed a positive association with CSF Aβ42 and Aβ42/40 ratio in APOE ε4 carriers and in the aMCI-AD subgroup.
- No significant associations were found between KL-VSHET and tau biomarkers or NfL.
- Serum sαKl was negatively associated with P-tau181 in aMCI-AD and positively with Aβ42/40 in APOE ε4 non-carriers.
Conclusions
- KL-VSHET may confer protection against amyloid pathology in AD, particularly in APOE ε4 carriers and individuals with aMCI-AD.
- sαKl exhibits complex associations with AD biomarkers, varying by clinical status and APOE genotype.
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