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

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Abstract
Background: Abnormal immunity in the periphery has been reported in the pathogenesis of Alzheimer's disease (AD). Objective: 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-related pathophysiology. Methods: The sample included 63 participants from a complete enumeration study of elderly people in Nakayama town (the Nakayama Study), who were over 65 years of age, diagnosed as (1) healthy controls (N = 21, mean age: 83.8 years), (2) having MCI due to AD (N = 20, mean age: 82.6 years), or (3) having AD (N = 21, mean age: 84.2 years). Every participant underwent blood tests, magnetic resonance imaging, and questionnaires about lifestyle and cognitive function. With transcriptome analysis, differential gene expressions in the blood of the three groups were evaluated by gene ontology, pathway enrichment, and ingenuity pathway analyses, and quantitative real-time PCR was performed. Results: 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. Conclusions: Based on these findings and consistent with other published studies, 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.
Funding Information
  • Japan Agency for Medical Research and Development (JP22dk0207053)
  • Japan Society for the Promotion of Science London (20K07971)
  • Japan Society for the Promotion of Science London (22K07597)
  • Japan Society for the Promotion of Science London (22K07562)
  • Japan Society for the Promotion of Science London (22K15752)
  • Japan Society for the Promotion of Science London (22K15765)
  • Japan Society for the Promotion of Science London (23K07016)

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