Alpha-Synuclein Seed Amplification Assay in CSF, Skin, and Submandibular Gland From Incidental Lewy Body Disease and Parkinson Disease.

Abstract (English)

BACKGROUND AND OBJECTIVES: Using RT-QuIC seeding assays determine the presence of pathogenic alpha-synuclein (aSyn) aggregates in the submandibular gland (SMG), skin, and CSF from autopsy-confirmed cases of incidental Lewy body disease (ILBD), Parkinson disease (PD), and controls. METHODS: Submandibular gland, skin, and CSF samples from autopsied cases in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) were assayed using RT-QuIC methods. Correlations with the Unified Staging System for Lewy Body Disorders (USSLB) was performed. RESULTS: A total of 19 controls, 40 ILBD, and 15 PD cases were studied. While aSyn seeding assays were positive in all 3 tissues from ILBD cases, the sensitivity was much lower in the SMG (13/37, 35.1%) and skin (6/16, 37.5%) than in CSF (25/33, 75.8%). In PD sensitivity was good in all tissues: SMG (7/8, 87.5%), skin (7/8, 87.5%), and CSF (10/10, 100%), as was specificity in CSF (9/12, 75%), skin (8/9, 88.9%), and SMG (7/9, 77.8%). USSLB stage correlated with aSyn SAA positivity in all 3 tissues with CSF most sensitive to stages I and II (IIa and IIb) cases. In the 20 cases that had all 3 tissues tested only 2 were positive in the SMG but not CSF and one in skin but not CSF. There were 6 ILBD cases that had positive CSF but not SMG or skin, and one of these ILBD cases was USSLB stage I (olfactory bulb only). DISCUSSION: In this small study of autopsy-confirmed ILBD, aSyn seeding assays had moderately high sensitivity (75.8%) in the CSF but not in skin or SMG. In PD, the skin, SMG, and CSF showed high sensitivity, with specificity being similar in all tissues, although sample sizes were small. These results, although preliminary, suggest that detecting aSyn using seeding assays of CSF, but not the skin or SMG, may be valuable for identifying individuals with prodromal Lewy body disease. This is especially true for ILBD cases that often had Lewy bodies in the olfactory bulb only (USSLB Stage I) or in brainstem regions (Stage IIa), suggesting that detecting these cases may require CSF and not biopsies of the skin or SMG.