Missorting of plasma miRNAs in aging and Alzheimer's disease
Maria Čarna1, Jan S Novotny1, Neda Dragišić1
1International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Abstract:
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.
Insights
Aging and Alzheimer's disease (AD) involve microRNAs (miRNAs). In AD, circulating miRNAs are further downregulated and primarily found in extracellular vesicles, indicating a pathological worsening of aging processes.
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroscience
Background:
- Aging is a primary risk factor for Alzheimer's disease (AD).
- MicroRNAs (miRNAs) play a role in regulating aging.
- The circulating miRNA network's role in AD, beyond aging, requires investigation.
Purpose of the Study:
- To investigate the circulating miRNA network in Alzheimer's disease (AD) in the context of aging.
- To understand how miRNA dysregulation in AD differs from normal aging.
Main Methods:
- Analysis of plasma miRNA levels and their predicted localization.
- Examination of miRNA motifs related to extracellular vesicle (EV) loading and secretion.
- Comparison of circulating miRNA profiles in aging versus AD.
Main Results:
- Plasma miRNAs are downregulated in aging and predicted to be within extracellular vesicles (EVs).
- In AD, miRNAs show further downregulation and altered EV-loading/secretion motifs.
- AD-associated miRNAs are exclusively predicted to reside within EVs.
Conclusions:
- The circulating miRNA network in AD reflects an exacerbated aging process.
- Physiological miRNA-mediated suppression of AD pathology becomes insufficient in AD.
- EV-bound miRNAs are central to AD pathogenesis and aging-related decline.
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