The effect of C-reactive protein and interleukin-3 on mild cognitive impairment with <i>APOE</i> ɛ4

BackgroundThe apolipoprotein E ε4 allele (<i>APOE</i> ε4) and inflammation are associated with Alzheimer's disease (AD) pathology. Mild cognitive impairment (MCI) is considered the preclinical and early stage of AD. However, the comprehensive effects of <i>APOE</i> ε4 and inflammatory mediators on MCI patients with specific <i>APOE</i> ε4 genotypes remain poorly understood.ObjectiveOur study aimed to explore how different numbers of the <i>APOE</i> ε4 alleles affect plasma C-reactive protein (CRP) and interleukin-3 (IL-3) levels and their associations with brain structure.MethodsA total of 339 MCI patients from the Alzheimer's Disease Neuroimaging Initiative study were enrolled. We compared their plasma concentrations of CRP and IL-3, cognitive performance, and cerebrospinal fluid (CSF) AD biomarkers levels across different <i>APOE</i> ε4 genotypes. Structural magnetic resonance imaging was utilized to measure gray matter volume outcomes. Pearson correlation analysis was used to explore the associations between the above indicators.ResultsPlasma CRP levels increased in the <i>APOE</i> ε4 carriers, but IL-3 expression notably decreased, and the homozygous state is the most significant. A negative correlation between CRP and several cognitive abilities was observed only in <i>APOE</i> ε4 homozygotes. Additionally, a positive correlation between IL-3, cognitive scores, and CSF biomarker levels was confirmed only in <i>APOE</i> ε4 homozygotes. Imaging data demonstrated that the gray matter volume of the right middle frontal gyrus was associated with CRP only in <i>APOE</i> ε4 non-carriers.ConclusionsOur study demonstrated that peripheral inflammatory mediators' effect on cognitive function and brain structure in MCI patients differs based on their <i>APOE</i> ε4 allele carrier status.