Lewy body (LB) diseases are characterized by alpha-synuclein (AS) aggregates in the central nervous system (CNS). Involvement of the peripheral autonomic nervous system (pANS) is increasingly recognized, although less studied. The aim of this study was to systematically analyze the distribution and severity of AS pathology in the CNS and pANS. Detailed postmortem histopathological study of brain and peripheral tissues from 28 brain bank donors (10 with Parkinson's disease [PD], 5 with dementia with LB [DLB], and 13 with non-LB diseases including atypical parkinsonism and non-LB dementia). AS aggregates were found in the pANS of all 15 LB disease cases (PD, DLB) in stellate and sympathetic ganglia (100%), vagus nerve (86.7%), gastrointestinal tract (86.7%), adrenal gland and/or surrounding fat (53.3%), heart (100%), and genitourinary tract (13.3%), as well as in 1 case of incidental Lewy body disease (iLBD). A craniocaudal gradient of AS burden in sympathetic chain and gastrointestinal tract was observed. DLB cases showed higher amounts of CNS AS aggregates than PD cases, but this was not the case in the pANS. No pANS AS aggregates were detected in Alzheimer's disease (AD) cases with or without CNS AS aggregates. All pathologically confirmed LB disease cases including 1 case of iLBD had AS aggregates in the pANS with a craniocaudal gradient of pathology burden in sympathetic chain and gastrointestinal tract. AS was not detected in the pANS of any AD case. These findings may help in the search of peripheral AS aggregates in vivo for the early diagnosis of PD.

Objective:To investigate the expression of α-synuclein in colonic biopsies of patients with idiopathic REM sleep behavior disorder (iRBD) and address if α-synuclein immunostaining of tissue obtained via colonic biopsies holds promise as a diagnostic biomarker for prodromal Parkinson disease (PD).Methods:Patients with iRBD, patients with PD, and healthy controls were prospectively recruited to undergo colonic biopsies for comparison of α-synuclein immunoreactivity patterns between the groups by using 2 different antibodies.Results:There was no difference in colonic mucosal and submucosal immunostaining between groups using the 15G7 α-synuclein antibody, which was found in almost all participants enrolled in this study. By contrast, immunostaining for serine 129-phosphorylated α-synuclein (pSyn) in submucosal nerve fibers or ganglia was found in none of 14 controls but was observed in 4 of 17 participants with iRBD and 1 out of 19 patients with PD.Conclusions:The present findings of pSyn immunostaining of colonic biopsies in a substantial proportion of iRBD participants raise the possibility that this tissue marker may be a suitable candidate to study further as a prodromal PD marker in at-risk cohorts.