Extracellular Vesicle-Enriched miRNA-Biomarkers Show Improved Utility for Detecting Alzheimer's Disease Dementia and Medial Temporal Atrophy

富含细胞外囊泡的 miRNA 生物标志物在检测阿尔茨海默病痴呆和内侧颞叶萎缩方面显示出更好的效用

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作者:Yuek Ling Chai, Lea Strohm, Yanan Zhu, Rachel S L Chia, Joyce Ruifen Chong, Danesha Devini Suresh, Li Han Zhou, Heng Phon Too, Saima Hilal, Tomas Radivoyevitch, Edward H Koo, Christopher P Chen, Gunnar Heiko Dirk Poplawski

Background

Emerging diagnostic modalities suggest that miRNA profiles within extracellular vesicles (EVs) isolated from peripheral blood specimens may provide a non-invasive diagnostic alternative for dementia and neurodegenerative disorders. Given that EVs confer a protective environment against miRNA enzymatic degradation, the miRNAs enriched in the EV fraction of blood samples could serve as more stable and clinically relevant biomarkers compared to those obtained from serum.

Conclusions

This data indicates that miRNA profiling from EVs offers diagnostic superiority. This underscores the role of EVs as vectors harboring prognostic biomarkers for neurodegenerative disorders and suggests their potential in yielding novel biomarkers for AD diagnosis.

Methods

We compared 25 AD patients to 34 individuals who exhibited no cognitive impairments (NCI). Subjects were Singapore residents with Chinese heritage. miRNAs purified from serum versus blood-derived EVs were analyzed for associations with AD dementia and medial temporal atrophy detected by magnetic resonance imaging.

Objective

To compare miRNAs isolated from EVs versus serum in blood taken from Alzheimer's disease (AD) dementia patients and control cohorts.

Results

Compared to serum-miRNAs, we identified almost twice as many EV-miRNAs associated with AD dementia, and they also correlated more significantly with medial temporal atrophy, a neuroimaging marker of AD-brain pathology. We further developed combination panels of serum-miRNAs and EV-miRNAs with improved performance in identifying AD dementia. Dominant in both panels was miRNA-1290. Conclusions: This data indicates that miRNA profiling from EVs offers diagnostic superiority. This underscores the role of EVs as vectors harboring prognostic biomarkers for neurodegenerative disorders and suggests their potential in yielding novel biomarkers for AD diagnosis.

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