Lack of Tissue Oxygenation from Sleep Apnea Linked to Parkinson’s, Study Suggests

Lack of Tissue Oxygenation from Sleep Apnea Linked to Parkinson’s, Study Suggests

Lack of tissue oxygenation associated with episodes of upper airway obstruction in patients with obstructive sleep apnea syndrome (OSAS) may increase the levels of alpha-synuclein in the blood and may contribute to the development of Parkinson’s disease, a study says.

The study, “Plasma α‐synuclein levels are increased in patients with obstructive sleep apnea syndrome,” was published in the Annals of Clinical and Translational Neurology.

Parkinson’s disease mainly results from the gradual loss of dopaminergic neurons in the substantia nigra, a region of the brain responsible for controlling movement.

The disease also seems to be associated with overproduction of the protein alpha-synuclein in nerve cells of the brain. When this protein clumps together, it gives rise to small toxic deposits inside brain cells, called Lewy bodies, inflicting damage and eventually killing them.

Of note, alpha-synuclein phosphorylation — a chemical modification in which a phosphate group is added to the protein — is known to occur in Parkinson’s disease, and is thought to be a critical step in disease progression as it enhances alpha-synuclein’s toxicity, possibly by increasing the formation of alpha synuclein aggregates.

“Recent studies found that [obstructive sleep apnea] was a risk factor for PD [Parkinson’s disease] onset, and hypoxia [lack of oxygen] may have contributed to it. [In addition,] previous studies both in vitro and in vivo revealed that hypoxia is able to induce overexpression of alpha‐synuclein (…). However, the detail mechanism remains to be further investigated,” the researchers wrote.

In this study, a group of Chinese scientists investigated the relationship between lack of tissue oxygenation caused by episodes of upper airway obstruction during sleep, and the levels of alpha-synuclein in patients with OSAS.

OSAS occurs when the throat muscles intermittently relax and block upper airways during sleep.

The study enrolled 42 patients who had been diagnosed with OSAS (eight with mild, 16 with moderate and 18 with severe OSAS) and 46 age- and sex-matched individuals with simple snoring (controls). The levels of total and phosphorylated alpha-synuclein in the patients’ blood plasma were measured by Enzyme-Linked Immunosorbent Assay (ELISA), a technique that allows researchers to measure the amount of a specific protein of interest using an enzymatic reaction).

Results showed that patients with OSAS had significantly higher levels of both total (37.68 ng/ml vs 21.08 ng/ml) and phosphorylated (26.87 ng/ml vs 14.61 ng/ml) alpha-synuclein in the plasma compared to controls.

Moreover, correlation analyses revealed the levels of both total and phosphorylated alpha-synuclein were positively correlated with the apnea–hypopnea index (an index that measures the severity of sleep apnea) and the oxygen desaturation index (an index that measures the number of times oxygen levels dip below a given threshold during sleep).

Conversely, the levels of both total and phosphorylated alpha-synuclein in the plasma were negatively correlated with the lowest and mean oxyhemoglobin saturations — the fraction of hemoglobin (red blood cells) bound to oxygen relative to the total hemoglobin found in the blood.

“In summary, the present study found that increased alpha-synuclein levels in the plasma are correlated with the degree of hypoxia in OSAS, indicating that chronic hypoxia caused by OSAS may be involved in the pathogenesis [disease manifestations]” of Parkinson’s, the scientists concluded.

Joana holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. She is currently finishing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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Joana holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. She is currently finishing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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  1. Increased alpha synuclein in serum/plasma exosomes has also recently been associated with exposure to welding fumes which contain carbon monoxide (which causes tissue hypoxia) and manganese (which increases oxidative stress). Exposure to these known neurotoxicants has been associated with parkinsonism. This new study is yet one more piece of the puzzle indicating how a lifetime of environmental and occupational exposures to various risk factors can modify the subclinical neuropathological processes that ultimately influence age of onset of this debilitating neurodegenerative disease.

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