Stage-dependent nigral neuronal loss in incidental Lewy body and Parkinson's disease.
Identifieur interne : 000419 ( Main/Exploration ); précédent : 000418; suivant : 000420Stage-dependent nigral neuronal loss in incidental Lewy body and Parkinson's disease.
Auteurs : Anke A. Dijkstra [Pays-Bas] ; Pieter Voorn ; Henk W. Berendse ; Henk J. Groenewegen ; Annemieke J M. Rozemuller ; Wilma D J. Van De BergSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2014.
Descripteurs français
- Wicri :
- geographic : Pays-Bas.
English descriptors
- KwdEn :
- Aged, Aged, 80 and over, Analysis of Variance, Case-Control Studies, Cell Count, Cell Death, Disease Progression, Female, Humans, Lewy Body Disease (pathology), Male, Netherlands, Neurons (metabolism), Neurons (pathology), Parkinson Disease (pathology), Severity of Illness Index, Statistics as Topic, Substantia Nigra (pathology), alpha-Synuclein (metabolism).
- MESH :
- chemical , metabolism : alpha-Synuclein.
- geographic : Netherlands.
- metabolism : Neurons.
- pathology : Lewy Body Disease, Neurons, Parkinson Disease, Substantia Nigra.
- Aged, Aged, 80 and over, Analysis of Variance, Case-Control Studies, Cell Count, Cell Death, Disease Progression, Female, Humans, Male, Severity of Illness Index, Statistics as Topic.
Abstract
To gain a better understanding of the significance of α-synuclein pathological conditions during disease progression in Parkinson's disease, we investigated whether 1) nigral neuronal loss in incidental Lewy body disease and Parkinson's disease donors is associated with the local burden α-synuclein pathological conditions during progression of pathological conditions; 2) the burden and distribution of α-synuclein pathological conditions are related to clinical measures of disease progression. Post-mortem tissue and medical records of 24 Parkinson's disease patients, 20 incidental Lewy body disease donors, and 12 age-matched controls were obtained from the Netherlands Brain Bank for morphometric analysis. We observed a 20% decrease in nigral neuronal cell density in incidental Lewy body disease compared with controls. Nigral neuronal loss (12%) was already observed before the appearance α-synuclein aggregates. The progression from Braak α-synuclein stage 3 to 4 was associated with a significant decline in neuronal cell density (46%). Nigral neuronal loss increased with later Braak α-synuclein stages but did not vary across consecutive Braak α-synuclein stages. We observed a negative correlation between neuronal density and local α-synuclein burden in the substantia nigra of Parkinson's disease patients (ρ = -0.54), but no relationship with Hoehn & Yahr stage or disease duration. In conclusion, our findings cast doubt on the pathogenic role of α-synuclein aggregates in elderly, but do suggest that the severity of neurodegeneration and local burden of α-synuclein pathological conditions are closely coupled during disease progression in Parkinson's disease.
DOI: 10.1002/mds.25952
PubMed: 24996051
Affiliations:
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Dijkstra</name><affiliation wicri:level="3"><nlm:affiliation>Department of Anatomy and Neurosciences, section of Functional Neuroanatomy, VU University Medical Center, Amsterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Anatomy and Neurosciences, section of Functional Neuroanatomy, VU University Medical Center, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Voorn, Pieter" sort="Voorn, Pieter" uniqKey="Voorn P" first="Pieter" last="Voorn">Pieter Voorn</name></author><author><name sortKey="Berendse, Henk W" sort="Berendse, Henk W" uniqKey="Berendse H" first="Henk W" last="Berendse">Henk W. Berendse</name></author><author><name sortKey="Groenewegen, Henk J" sort="Groenewegen, Henk J" uniqKey="Groenewegen H" first="Henk J" last="Groenewegen">Henk J. Groenewegen</name></author><author><name sortKey="Rozemuller, Annemieke J M" sort="Rozemuller, Annemieke J M" uniqKey="Rozemuller A" first="Annemieke J M" last="Rozemuller">Annemieke J M. Rozemuller</name></author><author><name sortKey="Van De Berg, Wilma D J" sort="Van De Berg, Wilma D J" uniqKey="Van De Berg W" first="Wilma D J" last="Van De Berg">Wilma D J. Van De Berg</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24996051</idno><idno type="pmid">24996051</idno><idno type="doi">10.1002/mds.25952</idno><idno type="wicri:Area/PubMed/Corpus">000456</idno><idno type="wicri:Area/PubMed/Curation">000456</idno><idno type="wicri:Area/PubMed/Checkpoint">000421</idno><idno type="wicri:Area/Ncbi/Merge">004047</idno><idno type="wicri:Area/Ncbi/Curation">004047</idno><idno type="wicri:Area/Ncbi/Checkpoint">004047</idno><idno type="wicri:Area/Main/Merge">000419</idno><idno type="wicri:Area/Main/Curation">000419</idno><idno type="wicri:Area/Main/Exploration">000419</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Stage-dependent nigral neuronal loss in incidental Lewy body and Parkinson's disease.</title><author><name sortKey="Dijkstra, Anke A" sort="Dijkstra, Anke A" uniqKey="Dijkstra A" first="Anke A" last="Dijkstra">Anke A. Dijkstra</name><affiliation wicri:level="3"><nlm:affiliation>Department of Anatomy and Neurosciences, section of Functional Neuroanatomy, VU University Medical Center, Amsterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Anatomy and Neurosciences, section of Functional Neuroanatomy, VU University Medical Center, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Voorn, Pieter" sort="Voorn, Pieter" uniqKey="Voorn P" first="Pieter" last="Voorn">Pieter Voorn</name></author><author><name sortKey="Berendse, Henk W" sort="Berendse, Henk W" uniqKey="Berendse H" first="Henk W" last="Berendse">Henk W. Berendse</name></author><author><name sortKey="Groenewegen, Henk J" sort="Groenewegen, Henk J" uniqKey="Groenewegen H" first="Henk J" last="Groenewegen">Henk J. Groenewegen</name></author><author><name sortKey="Rozemuller, Annemieke J M" sort="Rozemuller, Annemieke J M" uniqKey="Rozemuller A" first="Annemieke J M" last="Rozemuller">Annemieke J M. Rozemuller</name></author><author><name sortKey="Van De Berg, Wilma D J" sort="Van De Berg, Wilma D J" uniqKey="Van De Berg W" first="Wilma D J" last="Van De Berg">Wilma D J. Van De Berg</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Analysis of Variance</term><term>Case-Control Studies</term><term>Cell Count</term><term>Cell Death</term><term>Disease Progression</term><term>Female</term><term>Humans</term><term>Lewy Body Disease (pathology)</term><term>Male</term><term>Netherlands</term><term>Neurons (metabolism)</term><term>Neurons (pathology)</term><term>Parkinson Disease (pathology)</term><term>Severity of Illness Index</term><term>Statistics as Topic</term><term>Substantia Nigra (pathology)</term><term>alpha-Synuclein (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="geographic" xml:lang="en"><term>Netherlands</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lewy Body Disease</term><term>Neurons</term><term>Parkinson Disease</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Analysis of Variance</term><term>Case-Control Studies</term><term>Cell Count</term><term>Cell Death</term><term>Disease Progression</term><term>Female</term><term>Humans</term><term>Male</term><term>Severity of Illness Index</term><term>Statistics as Topic</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>Pays-Bas</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">To gain a better understanding of the significance of α-synuclein pathological conditions during disease progression in Parkinson's disease, we investigated whether 1) nigral neuronal loss in incidental Lewy body disease and Parkinson's disease donors is associated with the local burden α-synuclein pathological conditions during progression of pathological conditions; 2) the burden and distribution of α-synuclein pathological conditions are related to clinical measures of disease progression. Post-mortem tissue and medical records of 24 Parkinson's disease patients, 20 incidental Lewy body disease donors, and 12 age-matched controls were obtained from the Netherlands Brain Bank for morphometric analysis. We observed a 20% decrease in nigral neuronal cell density in incidental Lewy body disease compared with controls. Nigral neuronal loss (12%) was already observed before the appearance α-synuclein aggregates. The progression from Braak α-synuclein stage 3 to 4 was associated with a significant decline in neuronal cell density (46%). Nigral neuronal loss increased with later Braak α-synuclein stages but did not vary across consecutive Braak α-synuclein stages. We observed a negative correlation between neuronal density and local α-synuclein burden in the substantia nigra of Parkinson's disease patients (ρ = -0.54), but no relationship with Hoehn & Yahr stage or disease duration. In conclusion, our findings cast doubt on the pathogenic role of α-synuclein aggregates in elderly, but do suggest that the severity of neurodegeneration and local burden of α-synuclein pathological conditions are closely coupled during disease progression in Parkinson's disease.</div></front></TEI><affiliations><list><country><li>Pays-Bas</li></country><region><li>Hollande-Septentrionale</li></region><settlement><li>Amsterdam</li></settlement></list><tree><noCountry><name sortKey="Berendse, Henk W" sort="Berendse, Henk W" uniqKey="Berendse H" first="Henk W" last="Berendse">Henk W. Berendse</name><name sortKey="Groenewegen, Henk J" sort="Groenewegen, Henk J" uniqKey="Groenewegen H" first="Henk J" last="Groenewegen">Henk J. Groenewegen</name><name sortKey="Rozemuller, Annemieke J M" sort="Rozemuller, Annemieke J M" uniqKey="Rozemuller A" first="Annemieke J M" last="Rozemuller">Annemieke J M. Rozemuller</name><name sortKey="Van De Berg, Wilma D J" sort="Van De Berg, Wilma D J" uniqKey="Van De Berg W" first="Wilma D J" last="Van De Berg">Wilma D J. Van De Berg</name><name sortKey="Voorn, Pieter" sort="Voorn, Pieter" uniqKey="Voorn P" first="Pieter" last="Voorn">Pieter Voorn</name></noCountry><country name="Pays-Bas"><region name="Hollande-Septentrionale"><name sortKey="Dijkstra, Anke A" sort="Dijkstra, Anke A" uniqKey="Dijkstra A" first="Anke A" last="Dijkstra">Anke A. Dijkstra</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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