Vagus Nerve and Stomach Synucleinopathy in Parkinson’s Disease, Incidental Lewy Body Disease, and Normal Elderly Subjects: Evidence Against the “Body-First” Hypothesis

Background: Braak and others have proposed that Lewy-type α-synucleinopathy in Parkinson’s disease (PD) may arise from an exogenous pathogen that passes across the gastric mucosa and then is retrogradely transported up the vagus nerve to the medulla. Objective: We tested this hypothesis by immunohis...

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Published inJournal of Parkinson's disease Vol. 11; no. 4; pp. 1833 - 1843
Main Authors Beach, Thomas G., Adler, Charles H., Sue, Lucia I., Shill, Holly A., Driver-Dunckley, Erika, Mehta, Shyamal H., Intorcia, Anthony J., Glass, Michael J., Walker, Jessica E., Arce, Richard, Nelson, Courtney M., Serrano, Geidy E.
Format Journal Article
LanguageEnglish
Published London, England SAGE Publications 01.01.2021
Sage Publications Ltd
Subjects
Aged
alpha-Synuclein
Autopsy
Carotid artery
Gastric mucosa
Humans
Hypotheses
Lewy bodies
Lewy body disease
Lewy Body Disease - pathology
Medulla oblongata
Movement disorders
Nervous system
Neurodegenerative diseases
Paraffin
Parkinson Disease - pathology
Parkinson's disease
Stomach
Stomach - pathology
Synuclein
Synucleinopathies
Vagus nerve
Vagus Nerve - pathology
gastrointestinal
Pathology
pathogenesis
peripheral nerve
autopsy
etiology
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Abstract Background: Braak and others have proposed that Lewy-type α-synucleinopathy in Parkinson’s disease (PD) may arise from an exogenous pathogen that passes across the gastric mucosa and then is retrogradely transported up the vagus nerve to the medulla. Objective: We tested this hypothesis by immunohistochemically staining, with a method specific for p-serine 129 α-synuclein (pSyn), stomach and vagus nerve tissue from an autopsy series of 111 normal elderly subjects, 33 with incidental Lewy body disease (ILBD) and 53 with PD. Methods: Vagus nerve samples were taken adjacent to the carotid artery in the neck. Stomach samples were taken from the gastric body, midway along the greater curvature. Formalin-fixed paraffin-embedded sections were immunohistochemically stained for pSyn, shown to be highly specific and sensitive for α-synuclein pathology. Results: Median disease duration for the PD group was 13 years. In the vagus nerve none of the 111 normal subjects had pSyn in the vagus, while 12/26 ILBD (46%) and 32/36 PD (89%) subjects were pSyn-positive. In the stomach none of the 102 normal subjects had pSyn while 5/30 (17%) ILBD and 42/52 (81%) of PD subjects were pSyn-positive. Conclusion: As there was no pSyn in the vagus nerve or stomach of subjects without brain pSyn, these results support initiation of pSyn in the brain. The presence of pSyn in the vagus nerve and stomach of a subset of ILBD cases indicates that synucleinopathy within the peripheral nervous system may occur, within a subset of individuals, at preclinical stages of Lewy body disease.
AbstractList Background: Braak and others have proposed that Lewy-type α-synucleinopathy in Parkinson’s disease (PD) may arise from an exogenous pathogen that passes across the gastric mucosa and then is retrogradely transported up the vagus nerve to the medulla. Objective: We tested this hypothesis by immunohistochemically staining, with a method specific for p-serine 129 α-synuclein (pSyn), stomach and vagus nerve tissue from an autopsy series of 111 normal elderly subjects, 33 with incidental Lewy body disease (ILBD) and 53 with PD. Methods: Vagus nerve samples were taken adjacent to the carotid artery in the neck. Stomach samples were taken from the gastric body, midway along the greater curvature. Formalin-fixed paraffin-embedded sections were immunohistochemically stained for pSyn, shown to be highly specific and sensitive for α-synuclein pathology. Results: Median disease duration for the PD group was 13 years. In the vagus nerve none of the 111 normal subjects had pSyn in the vagus, while 12/26 ILBD (46%) and 32/36 PD (89%) subjects were pSyn-positive. In the stomach none of the 102 normal subjects had pSyn while 5/30 (17%) ILBD and 42/52 (81%) of PD subjects were pSyn-positive. Conclusion: As there was no pSyn in the vagus nerve or stomach of subjects without brain pSyn, these results support initiation of pSyn in the brain. The presence of pSyn in the vagus nerve and stomach of a subset of ILBD cases indicates that synucleinopathy within the peripheral nervous system may occur, within a subset of individuals, at preclinical stages of Lewy body disease.
Background: Braak and others have proposed that Lewy-type α-synucleinopathy in Parkinson’s disease (PD) may arise from an exogenous pathogen that passes across the gastric mucosa and then is retrogradely transported up the vagus nerve to the medulla. Objective: We tested this hypothesis by immunohistochemically staining, with a method specific for p-serine 129 α-synuclein (pSyn), stomach and vagus nerve tissue from an autopsy series of 111 normal elderly subjects, 33 with incidental Lewy body disease (ILBD) and 53 with PD. Methods: Vagus nerve samples were taken adjacent to the carotid artery in the neck. Stomach samples were taken from the gastric body, midway along the greater curvature. Formalin-fixed paraffin-embedded sections were immunohistochemically stained for pSyn, shown to be highly specific and sensitive for α-synuclein pathology. Results: Median disease duration for the PD group was 13 years. In the vagus nerve none of the 111 normal subjects had pSyn in the vagus, while 12/26 ILBD (46%) and 32/36 PD (89%) subjects were pSyn-positive. In the stomach none of the 102 normal subjects had pSyn while 5/30 (17%) ILBD and 42/52 (81%) of PD subjects were pSyn-positive. Conclusion: As there was no pSyn in the vagus nerve or stomach of subjects without brain pSyn, these results support initiation of pSyn in the brain. The presence of pSyn in the vagus nerve and stomach of a subset of ILBD cases indicates that synucleinopathy within the peripheral nervous system may occur, within a subset of individuals, at preclinical stages of Lewy body disease.
Braak and others have proposed that Lewy-type α-synucleinopathy in Parkinson's disease (PD) may arise from an exogenous pathogen that passes across the gastric mucosa and then is retrogradely transported up the vagus nerve to the medulla. We tested this hypothesis by immunohistochemically staining, with a method specific for p-serine 129 α-synuclein (pSyn), stomach and vagus nerve tissue from an autopsy series of 111 normal elderly subjects, 33 with incidental Lewy body disease (ILBD) and 53 with PD. Vagus nerve samples were taken adjacent to the carotid artery in the neck. Stomach samples were taken from the gastric body, midway along the greater curvature. Formalin-fixed paraffin-embedded sections were immunohistochemically stained for pSyn, shown to be highly specific and sensitive for α-synuclein pathology. Median disease duration for the PD group was 13 years. In the vagus nerve none of the 111 normal subjects had pSyn in the vagus, while 12/26 ILBD (46%) and 32/36 PD (89%) subjects were pSyn-positive. In the stomach none of the 102 normal subjects had pSyn while 5/30 (17%) ILBD and 42/52 (81%) of PD subjects were pSyn-positive. As there was no pSyn in the vagus nerve or stomach of subjects without brain pSyn, these results support initiation of pSyn in the brain. The presence of pSyn in the vagus nerve and stomach of a subset of ILBD cases indicates that synucleinopathy within the peripheral nervous system may occur, within a subset of individuals, at preclinical stages of Lewy body disease.
Author Shill, Holly A.
Sue, Lucia I.
Arce, Richard
Walker, Jessica E.
Serrano, Geidy E.
Driver-Dunckley, Erika
Mehta, Shyamal H.
Nelson, Courtney M.
Beach, Thomas G.
Glass, Michael J.
Adler, Charles H.
Intorcia, Anthony J.
AuthorAffiliation b Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ
a Banner Sun Health Research Institute, Sun City, AZ
c Barrow Neurological Institute, Phoenix, AZ
AuthorAffiliation_xml – name: a Banner Sun Health Research Institute, Sun City, AZ
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/34151862$$D View this record in MEDLINE/PubMed
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Snippet Background: Braak and others have proposed that Lewy-type α-synucleinopathy in Parkinson’s disease (PD) may arise from an exogenous pathogen that passes across...
Background: Braak and others have proposed that Lewy-type α-synucleinopathy in Parkinson’s disease (PD) may arise from an exogenous pathogen that passes across...
Braak and others have proposed that Lewy-type α-synucleinopathy in Parkinson's disease (PD) may arise from an exogenous pathogen that passes across the gastric...
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SubjectTerms Aged
alpha-Synuclein
Autopsy
Carotid artery
Gastric mucosa
Humans
Hypotheses
Lewy bodies
Lewy body disease
Lewy Body Disease - pathology
Medulla oblongata
Movement disorders
Nervous system
Neurodegenerative diseases
Paraffin
Parkinson Disease - pathology
Parkinson's disease
Stomach
Stomach - pathology
Synuclein
Synucleinopathies
Vagus nerve
Vagus Nerve - pathology
Title Vagus Nerve and Stomach Synucleinopathy in Parkinson’s Disease, Incidental Lewy Body Disease, and Normal Elderly Subjects: Evidence Against the “Body-First” Hypothesis
URI https://journals.sagepub.com/doi/full/10.3233/JPD-212733
https://www.ncbi.nlm.nih.gov/pubmed/34151862
https://www.proquest.com/docview/2581172504
https://pubmed.ncbi.nlm.nih.gov/PMC10082635
Volume 11
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