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Alpha-synuclein pathology in Parkinson's and Alzheimer's disease brain: incidence and topographic distribution--a pilot study.
Acta Neuropathol. 2003 Sep; 106(3):191-201.AN

Abstract

To study the incidence and topographic distribution of alpha-synuclein-positive inclusions in Parkinson's disease (PD), dementia with LB (DLB), and Alzheimer's disease (AD), 206 brains of elderly patients, including 53 patients with clinical PD, 110 autopsy-proven AD cases, 22 with dementia with LB (DLB), 1 case with essential tremor, and 20 age-matched controls were investigated using alpha-synuclein immunohistochemistry. For technical reasons, the olfactory system was not studied. In all PD brains, alpha-synuclein-positive inclusions and neuronal losses were present in medullary and pontine nuclei, locus coeruleus, and substantia nigra, with additional lesions in amygdala (24%), allocortex (58%), cingulate area (34%), and isocortex (26.5%). All PD cases corresponded to pathology stage 4-6 suggested by Braak et al. (2003, Neurobiol Aging 24:197). In most cases of DLB, the distribution of alpha-synuclein pathology and neurodegeneration corresponded to stages 5 and 6 of PD pathology. The case with essential tremor and 48.2% of the AD cases showed no LB pathology; in the other AD brains alpha-synuclein-positive inclusions were seen in various brain areas. None of the controls showed LB pathology. Among 12 cases of incidental Lewy body disease (without clinical parkinsonian signs), 7 corresponded morphologically to PD stage 3 or 4. In further 6 AD cases, 2 with parkinsonian symptoms, considerable damage to locus coeruleus, substantia nigra, nucleus basalis and allocortex with preservation of the medullary nuclei was seen. The preliminary data largely confirm the Braak staging of brain pathology, although some of the clinical PD cases corresponded to stage 3 often considered as "preclinical". In addition, some cases without demonstrable involvement of medullary nuclei showed extensive PD-like pathology in other brain areas, suggesting deviation from the proposed stereotypic expansion pattern and that incidental LB pathology may affect solely the locus coeruleus and substantia nigra. Striking similarity of LB pathology between DLB and PD suggests close morphological relationship between both disorders. Widespread LB lesions occurred in many sporadic AD cases without parkinsonian symptoms, the pathogenesis and clinical impact of which are unclear. The relationship between AD and PD with particular reference to alpha-synuclein-positive lesions needs further elucidation [corrected].

Authors+Show Affiliations

Institute of Clinical Neurobiology, Kenyongasse 18, 1070 Vienna, Austria. kurt.jellinger@univie.ac.at

Pub Type(s)

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

Language

eng

PubMed ID

12845452

Citation

Jellinger, Kurt A.. "Alpha-synuclein Pathology in Parkinson's and Alzheimer's Disease Brain: Incidence and Topographic Distribution--a Pilot Study." Acta Neuropathologica, vol. 106, no. 3, 2003, pp. 191-201.
Jellinger KA. Alpha-synuclein pathology in Parkinson's and Alzheimer's disease brain: incidence and topographic distribution--a pilot study. Acta Neuropathol. 2003;106(3):191-201.
Jellinger, K. A. (2003). Alpha-synuclein pathology in Parkinson's and Alzheimer's disease brain: incidence and topographic distribution--a pilot study. Acta Neuropathologica, 106(3), 191-201.
Jellinger KA. Alpha-synuclein Pathology in Parkinson's and Alzheimer's Disease Brain: Incidence and Topographic Distribution--a Pilot Study. Acta Neuropathol. 2003;106(3):191-201. PubMed PMID: 12845452.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alpha-synuclein pathology in Parkinson's and Alzheimer's disease brain: incidence and topographic distribution--a pilot study. A1 - Jellinger,Kurt A, Y1 - 2003/07/05/ PY - 2003/04/03/received PY - 2003/04/25/revised PY - 2003/04/25/accepted PY - 2003/7/8/pubmed PY - 2004/1/10/medline PY - 2003/7/8/entrez SP - 191 EP - 201 JF - Acta neuropathologica JO - Acta Neuropathol VL - 106 IS - 3 N2 - To study the incidence and topographic distribution of alpha-synuclein-positive inclusions in Parkinson's disease (PD), dementia with LB (DLB), and Alzheimer's disease (AD), 206 brains of elderly patients, including 53 patients with clinical PD, 110 autopsy-proven AD cases, 22 with dementia with LB (DLB), 1 case with essential tremor, and 20 age-matched controls were investigated using alpha-synuclein immunohistochemistry. For technical reasons, the olfactory system was not studied. In all PD brains, alpha-synuclein-positive inclusions and neuronal losses were present in medullary and pontine nuclei, locus coeruleus, and substantia nigra, with additional lesions in amygdala (24%), allocortex (58%), cingulate area (34%), and isocortex (26.5%). All PD cases corresponded to pathology stage 4-6 suggested by Braak et al. (2003, Neurobiol Aging 24:197). In most cases of DLB, the distribution of alpha-synuclein pathology and neurodegeneration corresponded to stages 5 and 6 of PD pathology. The case with essential tremor and 48.2% of the AD cases showed no LB pathology; in the other AD brains alpha-synuclein-positive inclusions were seen in various brain areas. None of the controls showed LB pathology. Among 12 cases of incidental Lewy body disease (without clinical parkinsonian signs), 7 corresponded morphologically to PD stage 3 or 4. In further 6 AD cases, 2 with parkinsonian symptoms, considerable damage to locus coeruleus, substantia nigra, nucleus basalis and allocortex with preservation of the medullary nuclei was seen. The preliminary data largely confirm the Braak staging of brain pathology, although some of the clinical PD cases corresponded to stage 3 often considered as "preclinical". In addition, some cases without demonstrable involvement of medullary nuclei showed extensive PD-like pathology in other brain areas, suggesting deviation from the proposed stereotypic expansion pattern and that incidental LB pathology may affect solely the locus coeruleus and substantia nigra. Striking similarity of LB pathology between DLB and PD suggests close morphological relationship between both disorders. Widespread LB lesions occurred in many sporadic AD cases without parkinsonian symptoms, the pathogenesis and clinical impact of which are unclear. The relationship between AD and PD with particular reference to alpha-synuclein-positive lesions needs further elucidation [corrected]. SN - 0001-6322 UR - https://www.unboundmedicine.com/medline/citation/12845452/Alpha_synuclein_pathology_in_Parkinson's_and_Alzheimer's_disease_brain:_incidence_and_topographic_distribution__a_pilot_study_ L2 - https://dx.doi.org/10.1007/s00401-003-0725-y DB - PRIME DP - Unbound Medicine ER -