Small nucleolar RNAs in plasma extracellular vesicles and their discriminatory power as diagnostic biomarkers of Alzheimer's disease

NEUROBIOLOGY OF DISEASE

卷:159

Article

Fitz, Nicholas F.¹  Wang, Jiebiao²  Kamboh, M. Ilyas³  Koldamova, Radosveta¹  Lefterov, Iliya¹ 

[1] Univ Pittsburgh, Sch Publ Hlth, Dept Environm & Occupat Hlth, Pittsburgh, PA 15261 USA

[2] Univ Pittsburgh, Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA

[3] Univ Pittsburgh, Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA

关键词: Alzheimer's disease;    Non-coding RNAs;    Extracellular vesicles;    snoRNA;    Diagnostic biomarkers;   

DOI  :  10.1016/j.nbd.2021.105481

来源: Elsevier

【 摘 要 】

The clinical diagnosis of Alzheimer's disease, at its early stage, remains a difficult task. Advanced imaging technologies and laboratory assays to detect A beta peptides A beta 42 and A beta 40, total and phosphorylated tau in CSF provide a set of biomarkers of developing AD brain pathology and facilitate the diagnostic process. The search for biofluid biomarkers, other than in CSF, and the development of biomarker assays have accelerated significantly and now represent the fastest-growing field in AD research. The goal of this study was to determine the differential enrichment of noncoding RNAs (ncRNAs) in plasma-derived extracellular vesicles (EV) of AD patients and Cognitively Normal controls (NC). Using RNA-seq, we profiled four significant classes of ncRNAs: miRNAs, snoRNAs, tRNAs, and piRNAs. We report a significant enrichment of SNORDs - a group of snoRNAs, in AD samples compared to NC. To verify the differential enrichment of two clusters of SNORDs - SNORD115 and SNORD116, localized on human chromosome 15q11-q13, we used plasma samples of an independent group of AD patients and NC. We applied ddPCR technique and identified SNORD115 and SNORD116 with a high discriminatory power to differentiate AD samples from NC. The results of our study present evidence that AD is associated with changes in the enrichment of SNORDs, transcribed from imprinted genomic loci, in plasma EV and provide a rationale to further explore the validity of those SNORDs as plasma biomarkers of AD.