Biopsy detects αSyn in submandibular gland of IRBD patients

By Lucy Piper

Submandibular gland biopsy can be used to identify α-synuclein (αSyn) aggregates, potentially offering not only a simple means of histologically confirming Parkinson's disease (PD) but also a marker for the disease in patients with premotor manifestations, researchers report.

Aggregates of αSyn were found by this method in 54% of the 45 patients studied, of whom 21 had idiopathic rapid-eye-movement sleep behaviour disorder (IRBD) and 24 PD. This compared with none of 26 control individuals (seven healthy, 11 undergoing neck surgery and eight autopsies).

"Core needle biopsy of the submandibular gland might be an option for the detection of αSyn because the gland is located subcutaneously, and is easy to localise by manual palpation or ultrasonography guidance", comments researcher Eduardo Tolosa (Hospital Clinic de Barcelona, Spain) and colleagues.

"Biopsy of the submandibular gland does not need general anaesthesia, is routinely done for diagnostic purposes [...], is less invasive than other procedures such as colonoscopy, and poses little risk to the patient", they add.

Material containing glandular parenchyma was obtained by transcutaneous core needle biopsy in nine of the 21 patients with IRBD, 12 of the 24 patients with PD and all 26 of the controls. And immunohistochemistry analysis showed the presence of αSyn aggregates in the nerve fibres of eight (89%) of the IRBD patients and eight (67%) of the PD patients, but in none of the controls.

Among the participants whose biopsy samples did not contain glandular parenchyma, but only muscular or connective tissue, αSyn aggregates were detected in these extraglandular tissues of an additional three (25%) of 12 patients with IRBD and five (42%) of 12 patients with PD. Again, none of the controls showed signs of αSyn in these tissues.

"Our observation that Lewy body type pathology is frequently found in the submandibular gland of patients with IRBD, but not in controls, provides in-vivo evidence that this sleep disorder is a manifestation of prodromal Parkinson's disease", the researchers write in The Lancet Neurology.

And it suggests that pathological changes in IRBD patients extend to a wider area beyond the brainstem nuclei that regulate rapid eye movement.

It is therefore possible that as well as being useful for histological confirmation of PD, αSyn detection in submandibular glands could serve as a marker for the disease in patients with IRBD and "might be useful for the design of disease-modifying strategies", say the researchers.

They caution, however, that "technical refinement is needed to implement the procedure in clinical and research settings. If this cannot be achieved, more accessible peripheral tissues (eg, skin or minor salivary glands) should be assessed with the aim of obtaining adequate histological samples."

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