Alpha-synuclein – a marker of the early stage of Parkinson’s disease

Exosomal Alpha-Synuclein – Biomarker of Parkinson’s Disease in Early Stages

Prerequisites for conducting research:Various biochemical markers of Parkinson’s disease, such as the level of homocysteine in peripheral blood, the level of dopamine transporter on lymphocyte membranes, and others have not found widespread use in clinical practice ( Fatemeh, 2018). The first motor manifestations of Parkinson’s disease occur when the amount of striatal dopamine decreases by 60-80%, and the number of dead nigrostriatal neurons reaches 60% of the initial level, which underscores the importance of early diagnosis of the disease ( Dauer, 2003). Brief Information:Alpha-synuclein is a protein found in various brain cells. The function of this substance is to regulate the intake and release of dopamine in nerve cells. It is the main component of Lewy bodies in Parkinson’s disease ( Spillantini, 1997). Lewy bodies are pathological formations in nerve cells, described in 1912 by F. Lewy, consisting of alpha-synuclein. In 1919, K. Tretyakov described them in the substantia nigra of patients with Parkinson’s disease ( Engelhardt, 2017). As they increase in size, Lewy bodies replace other important structures within brain cells, leading to disruption of their main functions. In people with Parkinson’s disease, exosomes are tiny vesicles secreted by neurons and other cells, involved in the transmission of misfolded proteins, including alpha-synuclein. Determining the amount of alpha-synuclein in blood serum can help diagnose Parkinson’s disease at the earliest stages and identify patients with different types of this disease. Alpha-synuclein is the main component of Lewy bodies, characteristic protein inclusions that accumulate in the brain cells of patients with Parkinson’s disease. In the early stages of Parkinson’s disease, tremor can occur both at rest and during movements, leading to misdiagnosis of essential tremor and incorrect therapy. Patients with Parkinson’s disease have lower levels of alpha-synuclein in the cerebrospinal fluid (the fluid surrounding the brain and spinal cord). However, measuring alpha-synuclein there was associated with the difficulty of material collection and the need for a spinal tap. Researchers hypothesized that exosomes formed in the brain and entering the bloodstream could be a peripheral biomarker of Parkinson’s disease. Scientists selected 38 patients with early-stage Parkinson’s disease who were recently diagnosed but had not yet received medication therapy.These patients were divided into groups:tremor-dominant (TD, 22 patients, average age 62.7 years, disease duration 19.2 months, age of onset 61.1 years), tremor-non-dominant (TND, 16 patients, average age 62.1 years, disease duration 35.8 months, age of onset 59.1 years). Comparison was made with 21 patients with confirmed diagnosis of essential tremor (average age 62 years) and 18 healthy volunteers.The results showed that in patients with Parkinson’s disease, the level of alpha-synuclein in exosomes was significantly lower than in patients with essential tremor and healthy volunteers P > 0.05). In the group of patients with Parkinson’s disease, the indicators also differed: in patients with the tremor-nondominant form of the disease (TND), characterized by more frequent development of depression and lack of motivation, the level of alpha-synuclein was lower than in patients with the tremor-dominant form P > 0.05).Thus, the obtained exosomal α-synuclein in blood serum can be considered a biomarker for detecting Parkinson’s disease at early stages, especially the TND forms of the disease, given the ease of collecting material for research (blood) and the complexity in differential diagnosis at the onset of the disease.Determining the level of alpha-synuclein in exosomes involved in its transmission in the brain is a biochemical marker of Parkinson’s disease at its early stages // Journal Neuroscience. 16.05.2019. URL: https://www.sciencedirect.com/research/article/abs/pii/S0306452219303318?via%3Dihub