Missorting of plasma miRNAs in aging and Alzheimer's disease

被引:1
作者
Carna, Maria [1 ]
Novotny, Jan S. [1 ]
Dragisic, Neda [1 ]
Slavik, Hanus [2 ,3 ]
Sheardova, Katerina [1 ,4 ,5 ]
Geda, Yonas E. [6 ]
Vyhnalek, Martin [1 ,7 ,8 ]
Laczo, Jan [1 ]
Hort, Jakub [1 ]
Mao, Zixu [9 ]
Rissman, Robert A. [10 ]
Hajduch, Marian [2 ]
Dammer, Eric B. [11 ]
Stokin, Gorazd B. [1 ,12 ,13 ]
机构
[1] St Annes Univ Hosp, Int Clin Res Ctr, Brno, Czech Republic
[2] Palacky Univ Olomouc, Inst Mol & Translat Med, Fac Med & Dent, Olomouc, Czech Republic
[3] Univ Hosp Olomouc, Dept Neurol, Olomouc, Czech Republic
[4] St Annes Univ Hosp, Dept Neurol 1, Brno, Czech Republic
[5] Masaryk Univ, Fac Med, Brno, Czech Republic
[6] Barrow Neurol Inst, Dept Neurobiol, Phoenix, AZ USA
[7] Charles Univ Prague, Fac Med 2, Dept Neurol, Prague, Czech Republic
[8] Motol Univ Hosp, Prague, Czech Republic
[9] Emory Univ, Dept Pharmacol & Chem Biol, Sch Med, Atlanta, GA USA
[10] Univ Calif San Diego, Dept Neurosci, La Jolla, CA USA
[11] Emory Univ, Dept Biochem, Sch Med, Atlanta, GA USA
[12] Univ Med Ctr, Div Neurol, Ljubljana, Slovenia
[13] Mayo Clin, Translat Aging & Neurosci Program, Rochester, MN USA
关键词
aging; Alzheimer's disease; endosomes; extracellular vesicles; miRNA; ncRNA; plasma; short sequence motifs; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; EXOSOME BIOGENESIS; MICRORNA; RNA; DEMENTIA; APP; RECOMMENDATIONS; EXPRESSION;
D O I
10.1111/jnc.15801
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The observation that aging is regulated by microRNAs (miRNA) and at the same time represents the greatest risk factor for Alzheimer's disease (AD), prompted us to examine the circulating miRNA network in AD beyond aging. We here show that plasma miRNAs in aging are downregulated and predicted to be preferentially targeted to the extracellular vesicle (EV) content. In AD, miRNAs are further downregulated, display altered proportions of motifs relevant to their loading into EVs and secretion propensity, and are forecast to be found exclusively in EVs. The circulating miRNA network in AD, therefore, reflects pathological exacerbation of the aging process whereby physiological suppression of AD pathology by miRNAs becomes insufficient.
引用
收藏
页码:149 / 161
页数:13
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