EXPRESSION OF SELECTED miRNAs IN CIRCULATING BLOOD OF EARLY AND LATE-ONSET ALZHEIMER DISEASE PATIENTS

Abstract

Objective: Inflammation and associated microRNAs (miRNA) both play essential roles in the pathogenesis of Alzheimer’s disease (AD). The expression profile of miRNA’s in an AD brain, also reflected in the peripheral blood mononuclear cells, may give support to the inflammatory changes seen in the course of AD. We aimed to investigate the expression levels of specific inflammatory miRNAs (mir-146a, mir-144, mir-34a) in both blood leukocytes and plasma of AD patients and to evaluate their potential usability as biomarkers in AD diagnosis and to also demonstrate whether the expression of these miRNAs differ between early and late-onset AD patients. Methods: We investigated the expression levels of miRNAs in 16 early-onset and 26 late-onset AD patients and in their respective controls by using qRT-PCR. Results: Plasma mir-144 levels were significantly different between EOAD and LOAD patients (p=0.015). In addition, levels of leukocyte mir-34a were significantly down-regulated in EOAD compared to LOAD patients (p=0.027). Our results also showed significant positive correlations between age and plasma mir- 144 and leukocyte mir-34a expressions. Conclusion: The differential expression of plasma mir-144 and leukocyte mir-34a between EOAD and LOAD patients might reflect age-dependent changes in miRNA expression and might be independent of the disease status.

Keywords

• Alzheimer disease
• miRNA
• miRNA expression

ERKEN VE GEÇ BAŞLANGIÇLI ALZHEIMER HASTALARININ PERİFERİK KANLARINDA SEÇİLMİŞ miRNA’LARIN ANLATIM DÜZEYİ

Abstract

Amaç: Enflamasyon ve ilişkili mikro RNA’lar (miRNA), Alzheimer hastalığının (AH) patogenezinde önemli rol oynamaktadırlar. AH beyininde görülen miRNA’ların anlatım profilindeki değişikliklerin periferal kan mononükleer hücrelerine de yansımış olması, AH sırasında görülen enflamatuar değişikliklerin bir göstergesi olabilir. Bu çalışmada, Alzheimer hastalarının hem periferal lökositlerinde hem de plazmalarında belirli enflamatuvar miRNA’ların (mir-146a, mir-144, mir-34a) anlatım düzeylerindeki değişiklikleri araştırmayı ve ve AH tanısında biyobelirteç olarak potansiyel kullanılabilirliklerini değerlendirmek. Ayrıca, bu miRNA’ların anlatımlarının erken ve geç başlangıçlı AH arasında farklılık gösterip göstermediğini belirlemeyi amaçladık. Gereç ve Yöntem: Gerçek zamanlı polimeraz zincir reaksiyonu yöntemini kullanarak 16 erken başlangıçlı ve 26 geç başlangıçlı AH hastası ve yaş-uyumlu kontrollerinde miRNA’ların anlatım düzeylerini araştırdık. Bulgular: Plazma mir-144 anlatım düzeyinin erken ve geç başlangıçlı AH hastaları arasında anlamlı farklılık gösterdiğini saptadık (p = 0.015). Ek olarak, lökosit mir-34a anlatım düzeyi erken başlangıçlı AH’de geç başlangıçlı AH hastalarına göre anlamlı derecede düşük bulundu (p = 0.027). Sonuçlarımız ayrıca, yaş ve plazma mir-144 (r=0.319, p=0.02) ile lökosit mir-34a (r=0.414, p=0.001) anlatım düzeyleri arasında anlamlı pozitif korelasyon olduğunu gösterdi. Sonuç: Bulgularımız erken ve geç başlangıçlı AH hastaları arasında plazma mir-144 ve lökosit mir-34a anlatımlarında görülen farklılığın miRNA ekspresyonundaki yaşa bağlı değişiklikleri yansıttığını ve hastalık durumundan bağımsız olabileceğini düşündürmektedir.

Keywords

• Alzheimer hastalığı
• miRNA
• miRNA anlatımı

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