Submandibular gland biopsy for the diagnosis of Parkinson disease

Abstract

The clinical diagnosis of Parkinson disease (PD) is incorrect in 30% or more of subjects particularly at the time of symptom onset. Because Lewy-type α-synucleinopathy is present in the submandibular glands of PD patients, we assessed the feasibility of submandibular gland biopsy for diagnosing PD. We performed immunohistochemical staining for Lewy-type α-synucleinopathy in sections of large segments (simulating open biopsy) and needle cores of submandibular glands from 128 autopsied and neuropathologically classified subjects, including 28 PD, 5 incidental Lewy body disease, 5 progressive supranuclear palsy (3 with concurrent PD), 3 corticobasal degeneration, 2 multiple system atrophy, 22 Alzheimer disease with Lewy bodies, 16 Alzheimer disease without Lewy bodies, and 50 normal elderly. Immunoreactive nerve fibers were present in large submandibular gland sections of all 28 PD subjects (including 3 that also had progressive supranuclear palsy); 3 Alzheimer disease with Lewy bodies subjects were also positive, but none of the other subjects were positive. Cores from frozen submandibular glands taken with 18-gauge needles (total length, 15-38 mm; between 10 and 118 sections per subject examined) were positive for Lewy-type α-synucleinopathy in 17 of 19 PD patients. These results suggest that biopsy of the submandibular gland may be a feasible means of improving PD clinical diagnostic accuracy. This would be particularly advantageous for subject selection in early-stage clinical trials for invasive therapies or for verifying other biomarker studies.

Figure 1

Phosphorylated α-synuclein-immunoreactive nerve fibers in large blocks (1–2 cm²) of submandibular gland from autopsied Parkinson disease (PD) patients. (A–F) Immunoreactive nerve fibers, some enlarged and distorted, within fascicles in the connective tissue stroma (A, B), closely applied to the smooth muscle layer of an arteriole (C), adjacent to a salivary ductule (D) and interweaving among serous gland cells (E, F). (G, H) Staining of gland cell cytoplasm was considered to be non-specific because it was seen in some subjects from all diagnostic categories; it is seen here in a PD case (G) and in a normal control (H). Scale bars: A, 250 μm; B, H, 35 μm; C, 60 μm; D, E, 150 μm; F, 75 μm; G, 40 μm.

Figure 2

Phosphorylated α-synuclein-immunoreactive nerve fibers in needle cores taken from frozen submandibular glands of autopsied Parkinson disease patients. (A) Low-magnification image of a typical tissue core. (B–D) Immunoreactive nerve fibers are most frequently seen within the connective tissue stroma. Panel (C) shows an immunoreactive nerve fiber near the peripheral surface of an arteriole. Scale bars: A, 1 mm; B, 100 μm; C, 50 μm; D, 150 μm.