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

BackgroundThe apolipoprotein E ε4 allele (APOE 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 APOE ε4 and inflammatory mediators on MCI patients with specific APOE ε4 genotypes remain poorly understood.ObjectiveOur study aimed to explore how different numbers of the APOE 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 APOE 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 APOE 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 APOE ε4 homozygotes. Additionally, a positive correlation between IL-3, cognitive scores, and CSF biomarker levels was confirmed only in APOE ε4 homozygotes. Imaging data demonstrated that the gray matter volume of the right middle frontal gyrus was associated with CRP only in APOE ε4 non-carriers.ConclusionsOur study demonstrated that peripheral inflammatory mediators' effect on cognitive function and brain structure in MCI patients differs based on their APOE ε4 allele carrier status.