Background. The presence of intraneuronal aggregates of phosphorylated alpha-synuclein (pAS), the histological hallmark of Parkinson disease (PD), has been already demonstrated to be present in the autonomic nerve fibres that innervate the submandibular gland in approximately 75% of living PD patients. The presence of pAS in the peripheral autonomic nervous system in carriers of LRRK2 mutations has not been studied so far. The objective of the current study is to evaluate the presence of abnormal pAS aggregates in the submandibular gland tissue of LRRK2 p.G2019S mutations carriers.
Methods. This is a prospective observational study conducted between 2014 and 2015 at Hospital Clínic de Barcelona, Spain. A random sample of nine asymptomatic LRRK2 (aLRRK2) and 11 LRRK2 associated PD (LRRK2-PD) patients were recruited among a cohort of LRRK2-PD patients and their relatives already identified at our centre. All the participants underwent transcutaneous needle core biopsy of the submandibular gland under ultrasound guidance. The presence of pAS was assessed in all the participants by immunohistochemistry using anti-Serine 129-phosphorylated AS antibody.
Results. Submandibular biopsy material containing glandular parenchyma was obtained in 4 (44.44%) aLRRK2 and in 6 (54.55%) LRRK2-PD patients. Aggregates of pAS were detected in the glandular parenchyma in one of the four (25%) aLRRK2 subjects and in none (0%) of the LRRK2-PD patients.
Conclusions. Our study shows that pAS aggregates obtained by needle core biopsy of the submandibular gland are infrequent in LRRK2 mutation carriers but may be detected in asymptomatic mutation carriers. The low rate of pAS positive biopsies suggests either a different physiopathology between LRRK2-related and idiopathic PD or that a one-time unilateral submandibular gland biopsy is not the optimal procedure for the study of synuclein aggregation in LRRK2 mutation carriers.