Blood RNA transcripts show changes in inflammation and lipid metabolism in Alzheimer’s disease and mitochondrial function in mild cognitive impairment

Abnormal immunity in the periphery appears to be involved in the pathogenesis of Alzheimer’s disease (AD). In this study, blood transcriptome analyses of patients with AD, those with mild cognitive impairment (MCI) due to AD, and heathy controls were performed to elucidate immune-mediated pathophysiology. The sample included 63 subjects from the Nakayama Study who were clinically diagnosed as (1) healthy controls (N=21), (2) having MCI due to AD (N=20), and (3) having AD (N=21). Blood samples were taken, magnetic resonance imaging was performed, and questionnaires were administered. RNA-seq, differential gene expression, gene ontology, pathway enrichment, and ingenuity pathway analyses were conducted, and polymerase chain reaction testing was performed. The results showed that neutrophil extracellular trap signaling was increased, and lipid metabolism (FXR/RXR activation, triacylglycerol degradation) was decreased in AD, whereas MCI showed protective responses via decreased neutrophil extracellular trap signaling and mitochondrial functions such as upregulation of the sirtuin pathway and downregulation of oxidative stress. Based on these findings, immune cells appear to have important roles in the pathogenesis of AD, and the transcriptome in blood may be useful as a biomarker for diagnosis via monitoring immunity in MCI and AD.