Alpha-Synuclein Lesions in the Peripheral Nervous System of the Larynx in Parkinson's Disease

Swallowing, speech and voice (SSV) disorders are very common in Parkinson's disease (PD). The aim of the present studies was to test our hypothesis that PD pathology affects the peripheral nervous system (PNS) of the larynx, thus possibly contributing to SSV deficits. Twenty-eight adult human larynges obtained from autopsied subjects with clinically diagnosed and neuropathologically confirmed PD (n = 20) and age-matched healthy controls (n = 8) were studied. Three laryngeal nerves (i.e., recurrent laryngeal nerve, RLN; external and internal superior laryngeal nerves, ESLN and ISLN), three muscles (i.e., thyroarytenoid, TA; posterior cricoarytenoid, PCA; and cricothyroid, CT), and three mucosa samples overlying the larynx and laryngopharynx (i.e., true vocal fold, TVF; laryngeal surface of the epiglottis, LSE; and aryepiglottic fold, AEF) were examined to detect phosphorylated α-synuclein (PAS) aggregates, the pathological hallmark of PD. The severity of the PAS lesions in the examined tissues was quantified by using a total PNS pathology score we newly developed. The results showed that the larynx was affected by PAS pathology in PD subjects but in none of the controls. The relative contributions of the PNS and brain pathologies to SSV disorders were analyzed. In this series, SSV severity levels in a substantial percentage (45%) of PD patients were more consistent with PNS than brain pathology severity levels. These findings suggest that in addition to brain pathology, PAS lesions in the PNS of the larynx also play an important role in the development of SSV disorders in PD.