Distribution of Proteinase K-resistant Anti-α-synuclein Immunoreactive Axons in the Cardiac Plexus is Unbiased to the Left Ventricular Anterior Wall

Overview

Journal Pathol Int

Specialty Pathology

Date 2023 Dec 1

PMID 38038140

Authors

Nei Fukasawa

Miku Maeda

Yoshifumi Sugiyama

Takahiro Fukuda

Masayuki Shimoda

Affiliations

Soon will be listed here.

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.

Citing Articles

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

Fukasawa N, Maeda M, Sugiyama Y, Fukuda T, Shimoda M Pathol Int. 2023; 74(1):1-12.

PMID: 38038140 PMC: 11551827. DOI: 10.1111/pin.13389.

References

Miki Y, Mori F, Wakabayashi K, Kuroda N, Orimo S . Incidental Lewy body disease restricted to the heart and stellate ganglia. Mov Disord. 2009; 24(15):2299-301. DOI: 10.1002/mds.22775. View

Fumimura Y, Ikemura M, Saito Y, Sengoku R, Kanemaru K, Sawabe M . Analysis of the adrenal gland is useful for evaluating pathology of the peripheral autonomic nervous system in lewy body disease. J Neuropathol Exp Neurol. 2007; 66(5):354-62. DOI: 10.1097/nen.0b013e3180517454. View

Dickson D, Fujishiro H, DelleDonne A, Menke J, Ahmed Z, Klos K . Evidence that incidental Lewy body disease is pre-symptomatic Parkinson's disease. Acta Neuropathol. 2008; 115(4):437-44. DOI: 10.1007/s00401-008-0345-7. View

Iwanaga K, Wakabayashi K, Yoshimoto M, Tomita I, Satoh H, Takashima H . Lewy body-type degeneration in cardiac plexus in Parkinson's and incidental Lewy body diseases. Neurology. 1999; 52(6):1269-71. DOI: 10.1212/wnl.52.6.1269. View

Wakabayashi K, Takahashi H . Neuropathology of autonomic nervous system in Parkinson's disease. Eur Neurol. 1997; 38 Suppl 2:2-7. DOI: 10.1159/000113469. View

Fujishiro H, Frigerio R, Burnett M, Klos K, Josephs K, DelleDonne A . Cardiac sympathetic denervation correlates with clinical and pathologic stages of Parkinson's disease. Mov Disord. 2008; 23(8):1085-92. DOI: 10.1002/mds.21989. View

Mitsui J, Saito Y, Momose T, Shimizu J, Arai N, Shibahara J . Pathology of the sympathetic nervous system corresponding to the decreased cardiac uptake in 123I-metaiodobenzylguanidine (MIBG) scintigraphy in a patient with Parkinson disease. J Neurol Sci. 2006; 243(1-2):101-4. DOI: 10.1016/j.jns.2005.11.034. View

Hawkes C, Del Tredici K, Braak H . Parkinson's disease: a dual-hit hypothesis. Neuropathol Appl Neurobiol. 2007; 33(6):599-614. PMC: 7194308. DOI: 10.1111/j.1365-2990.2007.00874.x. View

Cremades N, Cohen S, Deas E, Abramov A, Chen A, Orte A . Direct observation of the interconversion of normal and toxic forms of α-synuclein. Cell. 2012; 149(5):1048-59. PMC: 3383996. DOI: 10.1016/j.cell.2012.03.037. View

10.

Pirc K, Poklar Ulrih N . α-Synuclein interactions with phospholipid model membranes: Key roles for electrostatic interactions and lipid-bilayer structure. Biochim Biophys Acta. 2015; 1848(10 Pt A):2002-12. DOI: 10.1016/j.bbamem.2015.06.021. View

11.

Navarro-Otano J, Gelpi E, Mestres C, Quintana E, Rauek S, Ribalta T . Alpha-synuclein aggregates in epicardial fat tissue in living subjects without parkinsonism. Parkinsonism Relat Disord. 2012; 19(1):27-31. DOI: 10.1016/j.parkreldis.2012.07.005. View

12.

Fukasawa N, Fukuda T, Nagaoka M, Harada T, Takahashi H, Ikegami M . Aggregation and phosphorylation of α-synuclein with proteinase K resistance in focal α-synucleinopathy predominantly localized to the cardiac sympathetic nervous system. Neuropathol Appl Neurobiol. 2017; 44(3):341-344. DOI: 10.1111/nan.12422. View

13.

Orimo S, Amino T, Itoh Y, Takahashi A, Kojo T, Uchihara T . Cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy body disease. Acta Neuropathol. 2005; 109(6):583-8. DOI: 10.1007/s00401-005-0995-7. View

14.

Amino T, Orimo S, Itoh Y, Takahashi A, Uchihara T, Mizusawa H . Profound cardiac sympathetic denervation occurs in Parkinson disease. Brain Pathol. 2005; 15(1):29-34. PMC: 8095848. DOI: 10.1111/j.1750-3639.2005.tb00097.x. View

15.

McKeith I, Boeve B, Dickson D, Halliday G, Taylor J, Weintraub D . Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology. 2017; 89(1):88-100. PMC: 5496518. DOI: 10.1212/WNL.0000000000004058. View

16.

Bonini N, Giasson B . Snaring the function of alpha-synuclein. Cell. 2005; 123(3):359-61. DOI: 10.1016/j.cell.2005.10.017. View

17.

Fujiwara H, Hasegawa M, Dohmae N, Kawashima A, Masliah E, Goldberg M . alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol. 2002; 4(2):160-4. DOI: 10.1038/ncb748. View

18.

Gelpi E, Navarro-Otano J, Tolosa E, Gaig C, Compta Y, Rey M . Multiple organ involvement by alpha-synuclein pathology in Lewy body disorders. Mov Disord. 2014; 29(8):1010-8. DOI: 10.1002/mds.25776. View

19.

Miake H, Mizusawa H, Iwatsubo T, Hasegawa M . Biochemical characterization of the core structure of alpha-synuclein filaments. J Biol Chem. 2002; 277(21):19213-9. DOI: 10.1074/jbc.M110551200. View

20.

Kawano H, Ryozo Okada , Yano K . Histological study on the distribution of autonomic nerves in the human heart. Heart Vessels. 2003; 18(1):32-9. DOI: 10.1007/s003800300005. View