Plasma microRNA predict cognitive decline in Parkinson's disease

Area of Science:

• Neuroscience
• Biomarker Discovery
• Genomics

Background:

• Parkinson's disease (PD) is a common neurodegenerative disorder characterized by motor impairments and non-motor symptoms like cognitive decline.
• Current PD diagnosis relies on clinical motor symptoms, necessitating improved diagnostic tools reflecting its heterogeneous nature.
• MicroRNAs (miRNAs) are stable, blood-detectable biomarkers dysregulated in PD, making them promising candidates for reflecting disease phenotypes.

Purpose of the Study:

• To identify plasma microRNA biomarkers associated with cognitive abilities in Parkinson's disease patients.
• To establish a diagnostic framework for PD that incorporates cognitive decline using microRNA profiles.
• To investigate the relationship between plasma microRNA levels and cognitive status assessed by the Montreal Cognitive Assessment (MoCA).

Main Methods:

• Assessed plasma levels of 187 neurodegeneration-related microRNAs using custom TaqMan arrays.
• Analyzed cross-sectional (n=102) and longitudinal (n=26) cohorts, alongside post-mortem brain tissue (n=16).
• Utilized statistical models to identify microRNAs predictive of cognitive decline in PD, controlling for disease progression and age.

Main Results:

• Numerous microRNAs showed altered levels with increasing cognitive decline in PD, predominantly showing downregulation.
• miR-192-5p was consistently upregulated in plasma and downregulated in the superior frontal gyrus post-mortem.
• miR-151-3p and miR-192-5p demonstrated the strongest predictive model for differentiating cognitively normal PD patients from those with cognitive decline.

Conclusions:

• Plasma microRNAs are significantly altered in Parkinson's disease patients.
• Identified microRNAs, particularly miR-151-3p and miR-192-5p, can predict cognitive decline in PD.
• These plasma microRNAs hold potential as clinically useful biomarkers for early detection and monitoring of cognitive impairment in PD.