Peripheral Lewy body pathology in Parkinson's disease and incidental Lewy body disease: Four cases

Abstract

The accumulation of Lewy pathology (LP) within autonomic nervous system tissues has received increased attention recently as a possible induction site for Lewy neurodegeneration and a possible source of biopsy material for biomarkers of early Parkinson's disease (PD). Here, we describe LP accumulation within various tissues involving peripheral autonomic nervous system neurons in three PD cases and one case of incidental Lewy body disease. Findings highlight the value of examining pathology within functional neuroanatomical systems and particularly the importance of Lewy neurites (LNs) in the pathophysiology of PD.

Introduction

In 1912, Fritz Jacob Lewy described protein aggregates in the brains of patients with Parkinson's disease (PD) in several areas of the brain, including the dorsal vagal nucleus, locus coeruleus, and globus pallidus [1]. Some years later, Konstantin Trétiakoff named them Lewy bodies (LBs) and described them in the substantia nigra [2]. The substantia nigra was the focus of most neuropathological studies in PD until recently, when it was proposed that the pathological hallmarks of PD begin in the lower brainstem and in the olfactory system [3], [4], [5], [6]. These and other studies have highlighted the importance of pathology in the autonomic nervous system as an early induction site for the pathological progression of Lewy pathology (comprised of LBs and Lewy neurites, LNs) through the neuraxis [7], [8], [9], [10]. Newer studies of patients with PD have revealed that most have symptoms of autonomic dysfunction [11], [12] that are often the presenting symptom and are strongly correlated with quality of life [13], [14], [15].

In an effort to develop better ways to diagnose PD before patients lose sufficient nigrostriatal function to manifest the typical PD-related motor symptoms, there has been a greater emphasis on defining the autonomic dysfunction that occurs at the earliest stages of disease development. The focus has also shifted to the analysis of patients without motor PD in whom LP are found at autopsy, i.e., incidental Lewy body disease (ILBD) [5], [16], [17], [18], [19], [20], [21]. In this study, we report on the presence of LP in the autonomic nervous system of three PD cases and one ILBD case using alpha-synuclein immunohistochemistry in 100 μm thick tissue sections to visualize the morphology of LP.