Researchers Contemplate Salivary Alpha-Synuclein as Parkinson’s Biomarker

Alpha-synuclein in saliva may be a potential biomarker for Parkinson’s disease, according to a recent review article, but more research is necessary to determine its reliability as a possible screening approach.

The study with that finding, “Salivary alpha‑synuclein as a biomarker for Parkinson’s disease: a systematic review,” was published in the Journal of Neural Transmission.

In Parkinson’s, a protein called alpha-synuclein clumps together, creating insoluble fibrils (small fibers) that accumulate inside nerve cells. These aggregates, known as Lewy bodies, are harmful to cells, eventually leading to cellular death, which then contributes to the onset of disease-related symptoms.

Unfortunately, alpha-synuclein aggregates can be confirmed only during an autopsy examination, so current diagnosis relies on Parkinson’s-related clinical symptoms instead of objective tissue changes.

That is why researchers are seeking reliable molecular biomarkers that can distinguish Parkinson’s from other conditions, monitor disease progression, or provide insight about a patient’s response to a given therapeutic intervention.

Lewy bodies have been found in the salivary glands of early-stage Parkinson’s patients. “Salivary alpha-synuclein is an easily accessible biomarker for PD [Parkinson’s disease] with promising results,” the researchers wrote.

The team decided to summarize the current knowledge of salivary alpha-synuclein as a potential biomarker for Parkinson’s. They searched the U.S. National Library of Medicine’s MEDLINE database from 1970 to April 2019 for several keywords related to Parkinson’s diseasem including “alpha synuclein,” “Lewy body pathology,” “saliva,” and “biomarker.”

Based on all their established criteria, researchers identified 476 studies, of which only eight had data on salivary alpha-synuclein, totaling 1,240 participants.

Of the eight studies, three reported total salivary alpha-synuclein levels (i.e., including all forms of the protein) were significantly lower in Parkinson’s patients, compared to healthy individuals, but the remaining five indicated no association between total alpha-synuclein concentration in saliva and the neurodegenerative disorder.

“In some studies, total salivary [alpha-synuclein] was associated with demographic and clinical features; however, no consistent pattern emerged. In one study, total [alpha-synuclein] levels were associated with poor cognitive performance in [Parkinson’s disease] patients,” the investigators noted.

Alpha-synuclein can be found in various molecular and structural forms. Half of the studies analyzed showed that people with Parkinson’s had higher levels of salivary oligomeric (aggregated) alpha-synuclein and a higher oligomeric alpha-synuclein/total alpha-synuclein ratio, than controls.

Additionally, one study indicated multiple genetic variants could alter total salivary alpha-synuclein concentrations in Parkinson’s. Nonetheless, in all studies there were important limitations to the scientific protocol and the corresponding results that may have influenced its conclusions. Some of those confounding factors included problems with sample collection, sample contamination, inadequate sample storage, or difficulties performing the tests.

“Utilization of saliva in biomarker discovery has several advantages over other biofluids. For instance, in comparison to CSF [cerebrospinal fluid, the liquid surrounding the brain and spinal cord] or serum/plasma, human saliva is readily accessible and is easier and less invasive to collect in adequate quantities,” the researchers explained.

Because of the minimal risk the approach imposes on the patient, salivary biomarkers may enable monitoring how the disease progresses and the effects of treatments.

Although studies suggest a decrease in total, and an increase in oligomeric,  salivary alpha-synuclein levels, results lack consistency. For now, salivary alpha-synuclein tests have yet to be adopted in clinical practice.