Neuroinflammation, orchestrated by glial cells and mediated by cytokines, is now recognized as a pivotal pathogenic mechanism in Alzheimer’s disease (AD). However, the interplay between host genetic variations driving inflammatory responses and the resultant central or peripheral inflammatory milieu in AD susceptibility remains poorly defined. This study aimed to decode the crosstalk between functional polymorphisms in key cytokine genes and their corresponding serum cytokine levels in relation to AD risk. We performed a case-control investigation involving 160 patients with newly diagnosed, sporadic late-onset AD and 280 age- and gender-matched cognitively healthy controls. Four important cytokines from serum were quantified using high-sensitivity ELISA. Functional single nucleotide polymorphisms in the regulatory regions of their genes were genotyped using PCR-RFLP. AD patients exhibited significantly elevated concentrations of all above cytokines (all p < 0.001). Several SNPs were associated with altered AD risk (IL-1β -511 C/T; TNF-α -308 G/A; IL-10 -1082 G/A). This cross-sectional case-control study demonstrates that specific cytokine gene polymorphisms are associated with AD risk in this Chinese cohort, and these genetic variants correlate with altered serum cytokine levels. These findings suggest an association between host genetic variation in inflammatory genes and AD susceptibility, but do not establish causality. The observed elevations in peripheral cytokines may reflect systemic inflammation rather than AD-specific neuroinflammation.
Wang et al. (Wed,) studied this question.