ABCB1 Gene Polymorphisms and Their Contribution to Cognitive Decline in Mild Cognitive Impairment: A Next-Generation...

Area of Science:

• Genetics
• Neuroscience
• Molecular Biology

Background:

• The ABCB1 gene is vital for clearing amyloid-beta peptides and transporting cholesterol, suggesting its involvement in Alzheimer's disease pathogenesis.
• Mild cognitive impairment (MCI) is a precursor to Alzheimer's disease, and understanding its progression is crucial for early intervention.

Purpose of the Study:

• To investigate the association between ABCB1 gene polymorphisms and cognitive decline, specifically language function, in individuals with MCI.
• To explore the potential molecular mechanisms underlying the impact of ABCB1 polymorphisms on cognitive performance.

Main Methods:

• A longitudinal cohort study of 1005 participants (including AD, MCI, subjective cognitive decline, and controls) from the Czech Brain Aging Study.
• Next-generation sequencing to analyze the entire ABCB1 gene and comprehensive neuropsychological tests to assess cognitive function, including language.
• In silico analyses to predict the functional impact of identified polymorphisms on gene expression and regulation.

Main Results:

• Ten ABCB1 polymorphisms were significantly associated with cognitive performance, particularly language decline in amnestic MCI patients.
• In silico analyses indicated that some polymorphisms may alter transcription factor binding sites and exonic splicing enhancer generation.
• One polymorphism (rs55912869) was identified as a potential binding site for microRNA hsa-mir-3163.

Conclusions:

• ABCB1 gene polymorphisms play a significant role in cognitive decline, especially language impairment, in individuals with amnestic MCI.
• These polymorphisms may influence cognitive function through interactions with microRNAs, transcription factors, and alternative splicing, impacting ABCB1 gene expression and function.
• The findings suggest ABCB1 polymorphisms as potential biomarkers for predicting cognitive decline and as therapeutic targets in MCI and Alzheimer's disease.