Abstract
Many neurodegenerative diseases, such as Alzheimer's disease, Parkinson disease, vascular and frontotemporal dementias, as well as other chronic neurological pathologies, are characterized by slow development with a long asymptomatic period followed by a stage with mild clinical symptoms. As a consequence, these serious pathologies are diagnosed late in the course of a disease, when massive death of neurons has already occurred and effective therapeutic intervention is problematic. Thus, the development of screening tests capable of detecting neurodegenerative diseases during early, preferably asymptomatic, stages is a high unmet need. Since such tests are to be used for screening of large populations, they should be non-invasive and relatively inexpensive. Further, while subjects identified by screening tests can be further tested with more invasive and expensive methods, e.g., analysis of cerebrospinal fluid or imaging techniques, to be of practical utility screening tests should have high sensitivity and specificity. In this review, we discuss advantages and disadvantages of various approaches to developing screening tests based on analysis of circulating cell-free microRNA (miRNA). Applications of circulating miRNA-based tests for diagnosis of acute and chronic brain pathologies, for research of normal brain aging, and for disease and treatment monitoring are also discussed.
Highlights
There are several basic types of clinical tests: (i) genetic tests that help predict predisposition to a particular disease; (ii) screening tests, which are applied to a large population for early detection of a disease, preferably prior to its clinical manifestation; (iii) diagnostic tests, which are applied when a person has clinical symptoms of a disease or when the pathology has been detected by a screening test; (iv) predictive tests aimed to predict the disease outcome and drug sensitivity; and (v) disease and treatment monitoring tests
When miRNA arrays are used for initial miRNA screening, many tissue-enriched miRNA are not detectable and, as a consequence, ubiquitous miRNA, including miRNA associated with common pathologic processes such as carcinogenesis or inflammation, are often selected as potential biomarkers
These miRNA can successfully differentiate patients with a particular disease from healthy control subjects, but not necessarily from patients with similar pathologies of other organs, since it is highly likely that the plasma or serum levels of these miRNA will be affected in such patients
Summary
There are several basic types of clinical tests: (i) genetic tests that help predict predisposition to a particular disease; (ii) screening tests, which are applied to a large population for early detection of a disease, preferably prior to its clinical manifestation; (iii) diagnostic tests, which are applied when a person has clinical symptoms of a disease or when the pathology has been detected by a screening test; (iv) predictive tests aimed to predict the disease outcome and drug sensitivity; and (v) disease and treatment monitoring tests. When miRNA arrays are used for initial miRNA screening, many tissue-enriched miRNA are not detectable and, as a consequence, ubiquitous miRNA, including miRNA associated with common pathologic processes such as carcinogenesis or inflammation, are often selected as potential biomarkers. The use of brain-enriched miRNA for CNS disorders should increase biomarker specificity.
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