Salivary α‐Synuclein as a Candidate Biomarker of Parkinsonism in 22q11.2 Deletion Syndrome

Background 22q11.2 deletion syndrome (22q11.2DS) has been linked to an increased risk of early‐onset Parkinson's disease. However, the pathophysiological mechanisms underlying parkinsonism remain poorly understood. Objective The objective is to investigate salivary total α‐synuclein levels in 22q11.2DS patients with and without parkinsonian motor signs. Methods This cross‐sectional study included 10 patients with 22q11.2DS with parkinsonism (Park+), ten 22q11.2DS patients without parkinsonism (Park−), and 10 age and sex‐comparable healthy subjects (HS). Salivary and serum α‐synuclein levels were measured using enzyme‐linked immunosorbent assay. Results Salivary total α‐synuclein concentration was significantly lower in Park (+) patients than in Park (−) patients and HS ( P = 0.007). In addition, salivary α‐synuclein showed good accuracy in discriminating Park (+) from Park (−) patients (area under the curve = 0.86) and correlated with motor severity and cognitive impairment. Conclusion This exploratory study suggests that the parkinsonian phenotype of 22q11.2DS is associated with a reduced concentration of monomeric α‐synuclein in biological fluids.