MicroRNA biomarkers in cerebrospinal fluid and plasma are associated with reduced cognitive decline in Alzheimer's Disease

Abstract Background Despite the promising prospects of using microRNAs in Alzheimer's disease (AD) research, several challenges remain unresolved. Method Our study analyzed the changes in microRNA expression levels in cerebrospinal fluid (CSF) and plasma samples and their association with concurrent cognitive decline and hippocampal volume changes in patients with AD using the Alzheimer's Disease Neuroimaging Initiative database. Result We observed a significant decrease in plasma hsa‐mir‐125b‐5p levels (P=0.018), significant increase in plasma hsa‐mir‐26a‐5p levels (P=0.017), and significant decrease in mir‐185b‐5p levels in CSF (P=0.017). However, these microRNAs showed no significant differences between the control and AD groups across various ATN subtypes. Lower plasma hsa‐mir‐125b‐5p and hsa‐mir‐26a‐5p concentrations and CSF mir‐185b‐5p concentrations were associated with a faster increase in Alzheimer’s Disease Assessment Scale Cognition 13‐item scale scores (P= 0.011, P=0.009, P=0.018, respectively) and a decline in hippocampal volume (P=0.25, P=0.052, P=0.044, respectively), suggesting a potentially detrimental influence on cognitive and memory impairment in AD progression. CSF mir‐185b‐5p concentrations were positive for amyloid deposition (P= 0.0451, r=0.1754) and negative for fibrillar amyloid levels (P= 0.0392, r=‐0.1647), indicating their potential relevance in AD pathology and the development of AD. Conclusion These results highlight the role of CSF and plasma microRNA biomarkers in predicting cognitive and clinical decline in patients with AD.