Relationship Between CXCL8 and APOE Ɛ4 allele in Cerebrospinal Fluid Samples from Brazilian Older Adults

TL;DR

This study found that older Brazilian adults with the APOE Ɛ4 allele had lower levels of CXCL8 in cerebrospinal fluid, suggesting a link between this allele and neuroinflammation in Alzheimer's disease.

Contribution

The study identifies a novel negative association between APOE Ɛ4 allele and CXCL8 levels in Brazilian older adults.

Findings

APOE Ɛ4 carriers had significantly lower CSF CXCL8 levels compared to non-carriers.

A negative correlation was found between APOE Ɛ4 allele and CXCL8 levels in cerebrospinal fluid.

Linear regression confirmed a significant negative association between APOE Ɛ4 and CXCL8 after adjusting for age, sex, and education.

Abstract

In Alzheimer's disease (AD), inflammation is a critical factor in disease progression. Among the cytokines involved in AD pathology, Interleukin 8 (CXCL8) has emerged as an important biomarker of neuroinflammation. Recent studies have identified a strong association between CXCL8 and the ApoE gene, particularly in carriers of the Ɛ4 allele, providing valuable insights into the role of these biomarkers in the pathophysiology of Alzheimer's disease.

Determine the CXCL8 profile and its relationship with APOE allele Ɛ4 in a cohort of brazilian older adults.

One hundred and five older adults were enrolled and grouped based on APOE allele Ɛ4 status: APOE Ɛ4 carriers (n = 41) and non‐carriers (n = 64). Cerebrospinal fluid (CSF) samples were obtained via lumbar puncture, and levels of cytokines were assessed by the Luminex xMAP technique. Kendall correlation test between apoE allele Ɛ4 status and cytokines were performed. CXCL8 was prominently distinguished among the cytokines. Comparison between APOE Ɛ4 carriers and non‐carriers for CSF CXCL8 levels were explored using the Mann‐Whitney U‐test. Finally, to predict the influence of APOE Ɛ4 on CSF CXCL8 levels, linear regression models with logarithmic‐transformed variables were employed, adjusted for age, sex, formal education.

A significant negative correlation was found only between CSF CXCL8 levels and APOE Ɛ4 (r=‐0.193; p = 0.017). Furthermore, we observed a decreased CSF CXCL8 levels in Ɛ4 carriers compared to the non‐carriers group (U=1676.50; p = 0.017). We further explored these association using a linear regression model adjusted for sex, age, and formal education background, which revealed a negative significant association between CXCL8 levels and the presence of the Ɛ4 allele (ß= ‐ 0.217; p = 0.029).

A decrease in CXCL8 levels was found to be associated with both APOE Ɛ4 allele in older brazilian adults, suggesting that CXCL8 may play a role in the pathology of neuroinflammation due to AD.

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