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Stage-dependent nigral neuronal loss in incidental Lewy body and Parkinson's disease.
Mov Disord. 2014 Sep; 29(10):1244-51.MD

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.

Authors+Show Affiliations

Department of Anatomy and Neurosciences, section of Functional Neuroanatomy, VU University Medical Center, Amsterdam, the Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24996051

Citation

Dijkstra, Anke A., et al. "Stage-dependent Nigral Neuronal Loss in Incidental Lewy Body and Parkinson's Disease." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 29, no. 10, 2014, pp. 1244-51.
Dijkstra AA, Voorn P, Berendse HW, et al. Stage-dependent nigral neuronal loss in incidental Lewy body and Parkinson's disease. Mov Disord. 2014;29(10):1244-51.
Dijkstra, A. A., Voorn, P., Berendse, H. W., Groenewegen, H. J., Rozemuller, A. J., & van de Berg, W. D. (2014). Stage-dependent nigral neuronal loss in incidental Lewy body and Parkinson's disease. Movement Disorders : Official Journal of the Movement Disorder Society, 29(10), 1244-51. https://doi.org/10.1002/mds.25952
Dijkstra AA, et al. Stage-dependent Nigral Neuronal Loss in Incidental Lewy Body and Parkinson's Disease. Mov Disord. 2014;29(10):1244-51. PubMed PMID: 24996051.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stage-dependent nigral neuronal loss in incidental Lewy body and Parkinson's disease. AU - Dijkstra,Anke A, AU - Voorn,Pieter, AU - Berendse,Henk W, AU - Groenewegen,Henk J, AU - ,, AU - Rozemuller,Annemieke J M, AU - van de Berg,Wilma D J, Y1 - 2014/07/03/ PY - 2013/02/12/received PY - 2014/05/19/revised PY - 2014/06/02/accepted PY - 2014/7/5/entrez PY - 2014/7/6/pubmed PY - 2015/5/15/medline KW - Braak α-synuclein staging KW - Parkinson's disease KW - substantia nigra KW - α-synuclein SP - 1244 EP - 51 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 29 IS - 10 N2 - 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. SN - 1531-8257 UR - https://www.unboundmedicine.com/medline/citation/24996051/Stage_dependent_nigral_neuronal_loss_in_incidental_Lewy_body_and_Parkinson's_disease_ L2 - https://doi.org/10.1002/mds.25952 DB - PRIME DP - Unbound Medicine ER -