Plasma miRNAs associated with cognitive impairment and brain hypometabolism in individuals with mild cognitive impairment

Detecting practical biomarkers to facilitate early diagnosis of Alzheimer's disease (AD) before the onset of overt symptoms is crucial for clinicians to develop preventive and therapeutic strategies. There is substantial experimental evidence indicating the dysregulation of several microRNA (miRNA) expression levels in AD. They are known to play a crucial role in modulating critical intracellular signaling pathways associated with the core pathophysiological mechanisms of AD. In this cross-sectional study, we investigated the association of blood-based miRNAs as non-invasive, cost-effective biomarkers for the early stages of AD, focusing on their impact on cognitive decline and metabolism. All data were extracted from the Alzheimer's Disease Assessment Scale (ADNI) database. A total of 152 subjects were categorized into mild cognitive impairment (MCI) and control groups based on their clinical dementia rating (CDR) scores, and significant differences between these cohorts were explored. Our objective was to establish correlations between miRNA levels and cognitive impairment tests, such as the Alzheimer's disease assessment scale (ADAS), as well as hypometabolism indices using fluorodeoxyglucose (FDG)-positron emission tomography (PET) neuroimaging. Our findings revealed associations between hsa-miR-19a-3p and hsa-miR-16-5p with brain hypometabolism, and between hsa-miR-125b-5p and cognitive performance. While these observations suggest that specific miRNAs may reflect early AD-related changes, they require replication in larger, independent, biomarker-confirmed cohorts to assess their potential clinical utility.