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Salivary ATP13A2 is a potential marker of therapy-induced motor complications and is expressed by inclusions in submandibulary glands in Parkinson s disease

ABSTRACT: Highlights • Patients with motor complications, not the remainder of the patients, show quantifiable levels of salivary ATP13A2.• Patients with motor complications present high salivary ATP13A2 concentration relative to controls.• Salivary ATP13A2 content in patients with motor complications positively correlates with levodopa equivalent daily dose and MDS-UPDRS.• The submandibulary gland in PD patients contains ATP13A2-expressing rounded inclusions of 10–20 µm in diameter.• This is the first description of ATP13A2-expressing inclusions outside the nervous system in PD patients.

Background

ATP13A2 holds promise as biomarker for Parkinsońs disease (PD). No study has examined how salivary ATP13A2 is related to motor features in idiopathic PD.

Methods

Salivary ATP13A2 concentration was evaluated with ELISA, and statistical correlations of ATP13A2 level with PD parameters were examined. The dose intensity of the dopaminergic medication regimen was expressed as levodopa equivalent daily dose (LEDD). ATP13A2 expression on histological sections of submandibular glands was evaluated using immunohistochemistry.

Results

Salivary ATP13A2 was undetectable in many subjects (28 % of patients, 43.7 % of controls). However, all the patients with motor complications (n = 28) showed quantifiable levels of ATP13A2, that positively correlated with MDS-UPDRS (total, parts III and IV), and LEDD (p < 0.05). Dyskinetic patients showed the highest LEDD values (p < 0.05). The histological study revealed: a) ATP13A2 staining was very intense in duct cells and vascular endothelium, and b) two patterns of ATP13A2-positive deposits are observed: rounded inclusions of 10–20 µm in diameter located in the interlobular tissue of the patients, and amorphous aggregates inside duct lumen in controls and patients.

Conclusions

The sensitivity of the ELISA assay was a major limitation for quantifying ATP13A2. However, salivary ATP13A2 was detected in all patients with motor complications, where a direct relationship among ATP13A2 concentration, levodopa equivalent daily dose, and MDS-UPDRS was found. Therefore, salivary ATP13A2 might be a reliable index of therapy-induced motor complications. ATP13A2 was expressed by rounded inclusions in the submandibulary gland of patients. This is the first description of ATP13A2-positive inclusions outside the nervous system.

SUBMITTER: Fernandez-Espejo E

PROVIDER: S-EPMC9445999 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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