Blood immune response genes are correlated with brain glucose metabolism

Abstract

AbstractBackgroundImaging techniques such as positron emission tomography (PET) have been fundamental to develop our understanding about Alzheimer's disease (AD) underlying features. Evidence suggests that neuroinflammation plays a complex role in the pathophysiology of AD. Nevertheless, whether peripheral inflammation affects brain function remains to be defined. In this context, the integration of blood‐based measures and imaging modalities can facilitate the understanding of the periphery‐brain interface in AD. Here, we developed a method to integrate immune response‐related genes, derived from blood transcriptomics, with [18F] Fluorodeoxyglucose ([18F]FDG)‐PET imaging data. We hypothesized that the differential expression of immune‐related genes would be associated with brain metabolism as indexed by [18F]FDG‐PET signal.MethodBlood transcriptome profiles and imaging data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Differential gene expression analysis was performed in 99 Cognitively Unimpaired (CU) and 218 Cognitively Impaired (CI) individuals, whose differentially expressed genes (DEGs) underwent functional enrichment analysis Gene Ontology (GO). Immune‐related GO terms were clustered by semantic similarity using the GOSemSim method for biological processes ontology. All computations analysis were performed in the R statistical environment. Integration with [18F]FDG‐PET images was performed using voxel generalized linear regression (GLR) models considering the covariates age, gender, education, and APOE ε4 status (RMINC package).ResultsPeripheral blood cells transcriptome analysis identified 10 enriched GO terms associated with the immune response. For each term, the GLR models were used to calculate voxel‐wise associations between [18F]FDG and gene expression, resulting in a t‐statistical map. Figure 1 demonstrated the uncorrected statistically significant correlated voxels (t‐value > 2.0). At the voxel level, biological processes related to regulatory mechanisms of innate immunity presented a 32% Correspondence with [18F]FDG‐PET signal in the gray matter of the medial frontal‐orbital gyrus.ConclusionHere, we demonstrated a significant association between brain glucose metabolism and immune‐related blood DEGs. Our findings suggest that peripheral inflammation that occurs in AD patients might have an impact on [18F]FDG‐PET metabolism.