Distribution of proteinase K-resistant anti-α-synuclein immunoreactive axons in the cardiac plexus is unbiased to the left ventricular anterior wall

Abstract

Lewy body disease (LBD) is characterized by the appearance of Lewy neurites and Lewy bodies, which are predominantly composed of α-synuclein. Notably, the cardiac plexus (CP) is one of the main targets of LBD research. Although previous studies have reported obvious differences in the frequency of Lewy body pathology (LBP) in the CP, none of them have confirmed whether LBP preferably appears in any part of the CP. Thus, we aimed to clarify the emergence and/or propagation of LBP in the CP. In this study, 263 consecutive autopsy cases of patients aged ≥50 years were included, with one region per case selected from three myocardial perfusion areas (MPAs) and subjected to proteinase K and then immunohistochemically stained with anti-α-synuclein antibodies to assess LBP. We stained all three MPAs in 17 cases with low-density LBP and observed the actual distribution of LBP. LBP were identified in the CP in 20.2% (53/263) of patients. Moreover, we found that LBP may appear in only one region of MPAs, mainly in the young-old group (35.3% (6/17) of patients). These findings suggest that it is possible to underestimate LBP in the CP, especially in the young-old group, by restricting the search to only one of the three MPAs.

Keywords: Lewy body disease; cardiac plexus; α-synuclein.

Figure 1

Representative images of Lewy body pathology in the cardiac plexus. (a, b) Nerve fascicles distributed from the epicardium to the outer myocardium in hematoxylin and eosin‐stained sections. Swollen axons (a: arrow) containing pale acidophilic amorphous material were observed (pale bodies), with some of them having a strongly acidophilic core (b: arrows) (LBs). (c–e) Most PKRαS‐IR axons were observed as enlarged nerve axons in the nerve fascicles around coronary arterial branches and were distributed in the epicardium or outer myocardium (c, d). Perimysial positive axons (dots or short threads) were rarely observed (e). (f–h) PKRαS‐IR (f), AαS‐IR (g), and PαS‐IR images (h) of the same nerve fascicle in the serial sections. PKRαS‐IR images showed more axons with less conspicuous swollen axons than the those shown by AαS‐IR and PαS‐IR images (arrow heads). Scale bar = 20 μm (a, e), 50 μm (b, d, f–h) and 200 μm (c). AαS‐IR = anti‐aggregated‐α‐synuclein immunoreactive; LBs, Lewy bodies; PKRαS‐IR = proteinase K‐resistant anti‐α‐synuclein immunoreactive; PαS‐IR = anti‐phosphorylated‐α‐synuclein immunoreactive. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Representative cases in the semi‐quantitative assessment of Lewy body pathology distribution density. (a–c) Representative cases classified as Group A (a), Group B (b), and Group C (c) in the semi‐quantitative evaluation are presented. Cases exhibiting similar distributions and densities on these images were categorized into three groups. Group D comprised cases in which no PKRαS‐IR axons were identified in the selected slides. Images of axons belonging (a) to the right coronary artery region (b) and (c) to the left anterior descending artery region. The blue dots in each of the three loupe images indicate the position of the observed PKRαS‐IR axon. High magnification images of the numbered blue dots are shown in the respective numbered images (a‐1–4, b‐1–4, and c‐1–2). In panel (a), multiple PKRαS‐IR axons formed clusters within perivascular nerve fascicles in the epicardium (a‐1). Multiple PKRαS‐IR axons also formed clusters within nerve fascicles in the deep septum (a‐2) and myocardium (a‐3). In addition, perimysial PKRαS‐IR axons were identified (a‐4). In panel (b), the nerve fascicles containing PKRαS‐IR axons were found near the boundary between the myocardium and epicardium (b‐1 and 4) and in the epicardium (b‐2 and 3), showing a clear distribution bias toward the epicardium compared with panel (a). In panel (c), the distribution trend of PKRαS‐IR axons was similar to that shown in panel (b), but the number of PKRαS‐IR axons was <5 in the entire slide. Scale bar = 50 μm (a‐1–4, b‐1–4, and c‐1–2). LV = left ventricle; PKRαS‐IR = proteinase K‐resistant anti‐α‐synuclein immunoreactive; RV = right ventricle. [Color figure can be viewed at wileyonlinelibrary.com]