Peripheral Synucleinopathy in Early Parkinson's Disease: Submandibular Gland Needle Biopsy Findings

Charles H. Adler, Brittany Dugger, Joseph G. Hentz, Michael L. Hinni, David G. Lott, Erika Driver-Dunckley, Shyamal Mehta, Geidy Serrano, Lucia I. Sue, Amy Duffy, Anthony Intorcia, Jessica Filon, Joel Pullen, Douglas G. Walker, Thomas G. Beach

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Introduction: Finding a peripheral tissue biopsy site to diagnose early PD would be of value for clinical care, biomarker validation, and as research enrollment criteria. Whereas autopsy and advanced PD studies suggest that the submandibular gland is an important biopsy site, there are no studies in early PD. The aim of this study was to determine whether needle biopsy of the submandibular gland reveals Lewy type alpha-synucleinopathy in early PD. Methods: Twenty-five early PD (duration < 5 years) and 10 controls underwent transcutaneous needle core biopsies of the submandibular gland. Tissue was stained for phosphorylated alpha-synuclein, reviewed blind to clinical diagnosis, and only nerve element staining was considered positive. Results: Mean (standard deviation) age was 69.5 (8.3) for the PD group, 64.8 (8.0) years for controls, and disease duration 2.6 (1.1) years. Six PD and 1 control subject had inadequate glandular tissue. Positive staining was found in 14 of 19 (74%) PD and 2 of 9 (22%) control subjects. PD-positive and -negative cases did not differ clinically. Adverse events (mainly swelling and bruising) were common (77% of cases), but were minor and transient. Conclusions: Submandibular gland needle biopsies identified phosphorylated alpha-synuclein staining in 74% of early PD subjects. False positives may be true false positives or may represent prodromal PD. If confirmed in larger studies with eventual autopsy confirmation, the potential value of submandibular gland biopsies for early PD may be to aid in clinical trial inclusion/exclusion and eventually serve as a gold standard for biomarker studies short of autopsy confirmation.

Original languageEnglish (US)
Pages (from-to)250-256
Number of pages7
JournalMovement Disorders
Volume31
Issue number2
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

Submandibular Gland
Needle Biopsy
Parkinson Disease
Autopsy
alpha-Synuclein
Staining and Labeling
Biopsy
Biomarkers
Large-Core Needle Biopsy
Clinical Trials
Research

Keywords

  • biopsy
  • Parkinson's disease
  • submandibular gland
  • synuclein

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Adler, C. H., Dugger, B., Hentz, J. G., Hinni, M. L., Lott, D. G., Driver-Dunckley, E., ... Beach, T. G. (2016). Peripheral Synucleinopathy in Early Parkinson's Disease: Submandibular Gland Needle Biopsy Findings. Movement Disorders, 31(2), 250-256. https://doi.org/10.1002/mds.26476

Peripheral Synucleinopathy in Early Parkinson's Disease : Submandibular Gland Needle Biopsy Findings. / Adler, Charles H.; Dugger, Brittany; Hentz, Joseph G.; Hinni, Michael L.; Lott, David G.; Driver-Dunckley, Erika; Mehta, Shyamal; Serrano, Geidy; Sue, Lucia I.; Duffy, Amy; Intorcia, Anthony; Filon, Jessica; Pullen, Joel; Walker, Douglas G.; Beach, Thomas G.

In: Movement Disorders, Vol. 31, No. 2, 01.01.2016, p. 250-256.

Research output: Contribution to journalArticle

Adler, CH, Dugger, B, Hentz, JG, Hinni, ML, Lott, DG, Driver-Dunckley, E, Mehta, S, Serrano, G, Sue, LI, Duffy, A, Intorcia, A, Filon, J, Pullen, J, Walker, DG & Beach, TG 2016, 'Peripheral Synucleinopathy in Early Parkinson's Disease: Submandibular Gland Needle Biopsy Findings', Movement Disorders, vol. 31, no. 2, pp. 250-256. https://doi.org/10.1002/mds.26476
Adler, Charles H. ; Dugger, Brittany ; Hentz, Joseph G. ; Hinni, Michael L. ; Lott, David G. ; Driver-Dunckley, Erika ; Mehta, Shyamal ; Serrano, Geidy ; Sue, Lucia I. ; Duffy, Amy ; Intorcia, Anthony ; Filon, Jessica ; Pullen, Joel ; Walker, Douglas G. ; Beach, Thomas G. / Peripheral Synucleinopathy in Early Parkinson's Disease : Submandibular Gland Needle Biopsy Findings. In: Movement Disorders. 2016 ; Vol. 31, No. 2. pp. 250-256.
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abstract = "Introduction: Finding a peripheral tissue biopsy site to diagnose early PD would be of value for clinical care, biomarker validation, and as research enrollment criteria. Whereas autopsy and advanced PD studies suggest that the submandibular gland is an important biopsy site, there are no studies in early PD. The aim of this study was to determine whether needle biopsy of the submandibular gland reveals Lewy type alpha-synucleinopathy in early PD. Methods: Twenty-five early PD (duration < 5 years) and 10 controls underwent transcutaneous needle core biopsies of the submandibular gland. Tissue was stained for phosphorylated alpha-synuclein, reviewed blind to clinical diagnosis, and only nerve element staining was considered positive. Results: Mean (standard deviation) age was 69.5 (8.3) for the PD group, 64.8 (8.0) years for controls, and disease duration 2.6 (1.1) years. Six PD and 1 control subject had inadequate glandular tissue. Positive staining was found in 14 of 19 (74{\%}) PD and 2 of 9 (22{\%}) control subjects. PD-positive and -negative cases did not differ clinically. Adverse events (mainly swelling and bruising) were common (77{\%} of cases), but were minor and transient. Conclusions: Submandibular gland needle biopsies identified phosphorylated alpha-synuclein staining in 74{\%} of early PD subjects. False positives may be true false positives or may represent prodromal PD. If confirmed in larger studies with eventual autopsy confirmation, the potential value of submandibular gland biopsies for early PD may be to aid in clinical trial inclusion/exclusion and eventually serve as a gold standard for biomarker studies short of autopsy confirmation.",
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AU - Hinni, Michael L.

AU - Lott, David G.

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AU - Mehta, Shyamal

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AU - Sue, Lucia I.

AU - Duffy, Amy

AU - Intorcia, Anthony

AU - Filon, Jessica

AU - Pullen, Joel

AU - Walker, Douglas G.

AU - Beach, Thomas G.

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N2 - Introduction: Finding a peripheral tissue biopsy site to diagnose early PD would be of value for clinical care, biomarker validation, and as research enrollment criteria. Whereas autopsy and advanced PD studies suggest that the submandibular gland is an important biopsy site, there are no studies in early PD. The aim of this study was to determine whether needle biopsy of the submandibular gland reveals Lewy type alpha-synucleinopathy in early PD. Methods: Twenty-five early PD (duration < 5 years) and 10 controls underwent transcutaneous needle core biopsies of the submandibular gland. Tissue was stained for phosphorylated alpha-synuclein, reviewed blind to clinical diagnosis, and only nerve element staining was considered positive. Results: Mean (standard deviation) age was 69.5 (8.3) for the PD group, 64.8 (8.0) years for controls, and disease duration 2.6 (1.1) years. Six PD and 1 control subject had inadequate glandular tissue. Positive staining was found in 14 of 19 (74%) PD and 2 of 9 (22%) control subjects. PD-positive and -negative cases did not differ clinically. Adverse events (mainly swelling and bruising) were common (77% of cases), but were minor and transient. Conclusions: Submandibular gland needle biopsies identified phosphorylated alpha-synuclein staining in 74% of early PD subjects. False positives may be true false positives or may represent prodromal PD. If confirmed in larger studies with eventual autopsy confirmation, the potential value of submandibular gland biopsies for early PD may be to aid in clinical trial inclusion/exclusion and eventually serve as a gold standard for biomarker studies short of autopsy confirmation.

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