CircRNAs in Peripheral Blood: Potential Biomarkers for Alzheimer’s Disease?

Introduction: Circular RNAs (circRNAs) have emerged as potential biomarkers and regulatory molecules in Alzheimer’s disease (AD). While several circRNAs have been identified as dysregulated in AD brain tissue, their role in peripheral blood remains unclear. This study investigates the expression patterns of 15 selected AD-associated circRNAs in blood samples and their potential correlation with amyloid pathology and APOE4 genotype.

Methods: Blood samples were collected from 58 individuals with cognitive deficits, 28 of which had an amyloid pathology confirmed by PET imaging. Quantitative real-time PCR (qRT-PCR) was used to measure the expression of specific circRNAs previously identified in AD brain tissue and/or cerebrospinal fluid (CSF). Statistical analyses were performed to assess associations with amyloid status, age, sex, and APOE4 genotype.

Results: CircRTN4 levels were significantly elevated in amyloid-positive men compared to amyloid-negative controls. In amyloid-negative women, circRTN4 expression increased with age, particularly in APOE4 carriers. However, APOE4-positive men exhibited an inverse trend, with amyloid-positive individuals showing lower circRTN4 levels than their amyloid-negative counterparts. Similarly, circGPHN levels were higher in amyloid-positive men but showed an age-related increase only in amyloid-negative individuals. In APOE4-positive women without amyloid pathology, circGPHN expression was lower than in other groups.

Conclusion: These findings suggest that certain circRNAs exhibit distinct age, sex- and APOE4-dependent expression patterns in peripheral blood, which may differ from their regulation in brain tissue. While some circRNAs are elevated in amyloid-positive men, age-dependent changes in women suggest a complex interaction between neurodege neration, genetic risk, and peripheral biomarker dynamics. Further studies are needed to clarify whether these circRNAs serve as early indicators of AD or reflect compensatory mechanisms in disease progression.

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Artikel online veröffentlicht:
30. April 2025