Lewy pathology of the esophagus correlates with the progression of Lewy body disease: a Japanese cohort study of autopsy cases

Zen-Ichi Tanei,Shinya Tanaka,Tomio Arai,Shigeo Murayama,Atsuko Motoda,Shinji Ito,Yuko Saito,Renpei Sengoku,Mikihiro Yamazaki,Ito Kawakami,Yasuhiro Sakashita,Tomoyasu Matsubara,Masako Ikemura

doi:10.1007/s00401-020-02233-8

Abstract

Lewy body disease (LBD) is a spectrum of progressive neurodegenerative disorders characterized by the wide distribution of Lewy bodies and neurites in the central and peripheral nervous system (CNS, PNS). Clinical diagnoses include Parkinson’s disease (PD), dementia with Lewy bodies, or pure autonomic failure. All types of LBD are accompanied by non-motor symptoms (NMSs) including gastrointestinal dysfunctions such as constipation. Its relationship to Lewy body-related α-synucleinopathy (Lewy pathology) of the enteric nervous system (ENS) is attracting attention because it can precede the motor symptoms. To clarify the role of ENS Lewy pathology in disease progression, we performed a clinicopathological study using the Brain Bank for Aging Research in Japan. Five-hundred and eighteen cases were enrolled in the study. Lewy pathology of the CNS and PNS, including the lower esophagus as a representative of the ENS, was examined via autopsy findings. Results showed that one-third of older people (178 cases, 34%) exhibited Lewy pathology, of which 78 cases (43.8%) exhibited the pathology in the esophagus. In the esophageal wall, Auerbach’s plexus (41.6%) was most susceptible to the pathology, followed by the adventitia (33.1%) and Meissner’s plexus (14.6%). Lewy pathology of the esophagus was significantly associated with autonomic failures such as constipation (p < 0.0001) and among PNS regions, correlated the most with LBD progression (r = 0.95, p < 0.05). These findings suggest that the propagation of esophageal Lewy pathology is a predictive factor of LBD.

Highlights

Lewy body disease (LBD) is a neurodegenerative disorder in which Lewy bodies (LBs) and neurites appear in the central and peripheral nervous systems (CNS, PNS)
Pathology was found in 9 cases (5%), including 5 cases in which it was limited to the sympathetic ganglia (Supplementary Table 3, online resource)
The present study demonstrates the following: (1) one-third of older people exhibited Lewy pathology in the CNS and/or PNS (178/518: 34%); and (2) the incidence of Lewy pathology in the esophagus was 43.8% in LBD (78/178): 92.1% in PDD (Parkinson disease with dementia)/dementia with Lewy bodies (DLB) (35/38, Brain Bank for Aging Research (BBAR) LB stage 4–5), 75% in Parkinson’s disease (PD) (Parkinson disease without dementia) (6/8, stage 3), 35% in preclinical/prodromal LBD (36/103, stage 1–2), 3.4% in the earliest stage of LBD (1/29, stage 0.5), and zero in controls (0/340, stage 0), which correlated with the progression of the BBAR LB stage

Summary

Introduction

Lewy body disease (LBD) is a neurodegenerative disorder in which Lewy bodies (LBs) and neurites appear in the central and peripheral nervous systems (CNS, PNS). It is clinically diagnosed as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), or pure autonomic failure (PAF) [36, 44,45,46,47, 51,52,53, 86]. Gastrointestinal dysfunction—a primary NMS in PD—has recently been attracting attention because Lewy pathology in the enteric nervous system (ENS) can be a predictive marker for PD/DLB [40, 80, 81, 87]

Methods

Results

Conclusion