Salivary Gland Biopsy Detects Abnormal Alpha-Synuclein in Early Stages of Parkinson’s, Study Finds

A modified form of the alpha-synuclein protein can be found in the salivary gland tissue of Parkinson’s patients even in the early stages of the disease, suggesting the protein could be a potential biomarker for this neurodegenerative disorder, a study reports.

The study, “Nitrated alpha-synuclein in minor salivary gland biopsies in Parkinson’s disease,” was published in Neuroscience Letters.

Accumulation of alpha-synuclein, the main component of Parkinson’s disease hallmark Lewy bodies, is not limited to the brain but also occurs in the peripheral autonomic nervous system, which regulates (innervates) the viscera and gut, controlling breathing and digestion, for instance.

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

In Parkinson’s, there’s an imbalance between the production of free radicals (including oxygen and nitrogen molecules) and the ability of cells to detoxify them, which damages dopamine-producing neurons. This oxidative/nitrative stress is also known to provoke undesirable modifications in alpha-synuclein’s structure, and nitrated forms of the protein have been found in the brain, gastrointestinal tract, and blood cells of Parkinson’s patients.

Studies focusing on Parkinson’s biomarkers have suggested that patients’ salivary glands may contain a high concentration of alpha-synuclein; however, none of these studies investigated alpha-synuclein’s nitrated form.

In this study, researchers at the Beijing Tiantan Hospital in China decided to explore the presence of nitrated alpha-synuclein in minor salivary glands of Parkinson’s disease patients.

To do so, eight patients with idiopathic (of unknown cause) Parkinson’s disease in the early clinical stages, including four men and four women at a mean age of 50.75 years, and seven age-matched healthy individuals used as controls underwent a minor salivary gland biopsy. Peripheral tissue biopsy enables the assessment of tissue changes in Parkinson’s disease over a patient’s lifetime.

Results revealed that all patients had nitrated alpha-synuclein in their salivary gland tissue, while controls were all negative for the presence of the abnormal form of this protein. Alpha-synuclein positive structures were mainly located in the gland’s less irrigated connective tissue part.

Brain imaging showed patients had asymmetrical and reduced dopamine uptake in movement control brain centers, more specifically in the caudate nucleus and the putamen.

Because nitrated alpha-synuclein exists in the early stages of the disease, it could be a promising Parkinson’s biomarker. Easily accessible, minor salivary glands constitute an ideal site for abnormal protein detection.

Nonetheless, larger sample studies and those exploring nitrated alpha-synuclein in other tissues should be conducted, the researchers said.