Early detection of neurodegenerative diseases

As has been demonstrated in numerous studies, the development of neurodegenerative diseases, such as Alzheimer (AD), Parkinson (PD), Huntington diseases, vascular and frontotemporal (FTD) dementias, begins 10–20 y prior to the clinical manifestation. Although molecular mechanisms behind various neurodegenerative diseases are different, many processes, e.g., neurite retraction, dysfunction and destruction of synapses and ultimately neuronal death, are characteristic of neurodegeneration in general. AD is the most common and, thus, actively investigated neurodegenerative disease, for which diagnostic tools and therapeutic treatments are being developed. Recent failures of anti-AD therapies in late-stage clinical trials (including dimebon of Medivation and Pfizer, solanezumab of Eli Lilly and bapineuzumab of Pfizer and Johnson & Johnson) highlighted two important points associated with the development of effective treatment for AD: first, therapy in late stages of AD is ineffective, most likely due to massive neuronal death, which precedes symptoms of dementia; and second, detailed stratified analysis of clinical data reveals promising results for treatment of AD patients with earlier, mild stages of the disease. Two approaches were demonstrated to be effective for early detection of AD: PET scan for in vivo detection of β-amyloid depositions, and analysis of levels of β-amyloid protein 1–42, total tau protein and phosphorylated tau181P protein in the cerebrospinal fluid. It needs to be mentioned, however, that invasiveness and high cost of these approaches hinder their use for primary screening. Our paper describes a new approach for early detection of neurodegenerative diseases based on quantitative analysis of Early detection of neurodegenerative diseases Circulating brain-enriched microRNA