Prevalence of Submandibular Gland Synucleinopathy in Parkinson’s Disease, Dementia with Lewy Bodies and other Lewy Body Disorders

Article type: Research Article

Authors: Beach, Thomas G.^{a; *} | Adler, Charles H.^b | Serrano, Geidy^a | Sue, Lucia I.^a | Walker, D.G.^a | Dugger, Brittany N.^c | Shill, Holly A.^d | Driver-Dunckley, Erika^b | Caviness, John N.^b | Intorcia, Anthony^a | Filon, Jessica^a | Scott, Sarah^a | Garcia, Angelica^a | Hoffman, Brittany^a | Belden, Christine M.^a | Davis, Kathryn J.^a | Sabbagh, Marwan N.^d | and the Arizona Parkinson’s Disease Consortium

Affiliations: [a] Banner Sun Health Research Institute, Sun City, AZ, USA | [b] Mayo Clinic, Scottsdale, AZ, USA | [c] University of California at San Francisco, USA | [d] Barrow Neurological Institute, Phoenix, AZ, USA

Correspondence: [*] Correspondence to: Thomas G. Beach, Banner Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85351, USA. Tel.: +1 623 832 5643; Fax: +1 623 815 2960; E-mail: [email protected].

Abstract: Background: Clinical misdiagnosis, particularly at early disease stages, is a roadblock to finding new therapies for Lewy body disorders. Biopsy of a peripheral site might provide improved diagnostic accuracy. Previously, we reported, from both autopsy and needle biopsy, a high prevalence of submandibular gland synucleinopathy in Parkinson’s disease (PD). Here, we report on an extension of these studies to subjects with dementia with Lewy bodies (DLB) and other Lewy body disorders in 228 autopsied subjects from the Arizona Study of Aging and Neurodegenerative Disorders. Objective: To provide an estimate of the prevalence of histological synucleinopathy in the submandibular glands of subjects with PD and other Lewy body disorders. Methods: Submandibular gland sections from autopsied subjects were stained with an immunohistochemical method for α-synuclein phosphorylated at serine 129. Included were 146 cases with CNS Lewy-type synucleinopathy (LTS), composed of 46 PD, 28 DLB, 14 incidental Lewy body disease (ILBD), 33 Alzheimer’s disease with Lewy bodies (ADLB) and 2 with progressive supranuclear palsy and Lewy bodies (PSPLB). Control subjects included 79 normal elderly, 15 AD, 12 PSP, 2 conticobasal degeneration (CBD) and 2 multiple system atrophy (MSA). Results: Submandibular gland LTS was found in 42/47 (89%) of the PD subjects, 20/28 (71%) DLB, 4/33 (12%) ADLB and 1/9 (11%) ILBD subjects but none of the 110 control subjects. Conclusions: These results provide support for further clinical trials of in vivo submandibular gland diagnostic biopsy for PD and DLB. An accurate peripheral biopsy diagnosis would assist subject selection for clinical trials and could also be used to verify other biomarkers.

Keywords: Biopsy, diagnosis, clinical trial, biomarker, pathology, therapy

DOI: 10.3233/JPD-150680

Journal: Journal of Parkinson's Disease, vol. 6, no. 1, pp. 153-163, 2016