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Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies.
Brain Res. 1999 Oct 02; 843(1-2):53-61.BR

Abstract

The precursor of the non-Abeta-component of Alzheimer's disease (AD) amyloid (NACP, alpha-synuclein) aggregates into insoluble filaments of Lewy bodies (LBs) in Parkinson's disease (PD) and dementia with LBs (DLB). The microtubule-associated protein tau is an integral component of filaments of neurofibrillary tangles (NFTs). NFTs are occasionally found in brains of PD and DLB; however, the presence of NFTs or tau-epitopes within LB-containing neurons is rare. Double-immunofluorescence study and peroxidase-immunohistochemical study in serial sections, performed to examine the co-localization of tau- and NACP-epitopes in the brainstem of PD and DLB, demonstrated that four different epitopes of tau including phosphorylation-dependent and independent ones were present in a minority of LBs, but more often than previously considered. A tau (tau2)-epitope was localized to filaments in the outer layers of brainstem-type LBs by immunoelectron microscopy. Therefore, we conclude that tau is incorporated into filaments in certain LBs. Extensive investigation has enabled us to classify this co-localization into four types: type 1, LBs with ring-shaped tau-immunoreactivity; type 2, LBs surrounded by NFTs; type 3, NACP- and tau-immunoreactive filamentous and granular masses; and type 4, NACP- and tau-immunoreactive dystrophic neurites. This study raises a new question whether aggregation and hyperphosphorylation of tau in PD and DLB are triggered by the collapse of intraneuronal organization of microtubules due to NACP-filament aggregation in neuronal perikarya and axons.

Authors+Show Affiliations

Department of Ultrastructure and Histochemistry, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo, Japan. arima@prit.go.jpNo affiliation info availableNo 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

10528110

Citation

Arima, K, et al. "Cellular Co-localization of Phosphorylated Tau- and NACP/alpha-synuclein-epitopes in Lewy Bodies in Sporadic Parkinson's Disease and in Dementia With Lewy Bodies." Brain Research, vol. 843, no. 1-2, 1999, pp. 53-61.
Arima K, Hirai S, Sunohara N, et al. Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies. Brain Res. 1999;843(1-2):53-61.
Arima, K., Hirai, S., Sunohara, N., Aoto, K., Izumiyama, Y., Uéda, K., Ikeda, K., & Kawai, M. (1999). Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies. Brain Research, 843(1-2), 53-61.
Arima K, et al. Cellular Co-localization of Phosphorylated Tau- and NACP/alpha-synuclein-epitopes in Lewy Bodies in Sporadic Parkinson's Disease and in Dementia With Lewy Bodies. Brain Res. 1999 Oct 2;843(1-2):53-61. PubMed PMID: 10528110.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies. AU - Arima,K, AU - Hirai,S, AU - Sunohara,N, AU - Aoto,K, AU - Izumiyama,Y, AU - Uéda,K, AU - Ikeda,K, AU - Kawai,M, PY - 1999/10/21/pubmed PY - 1999/10/21/medline PY - 1999/10/21/entrez SP - 53 EP - 61 JF - Brain research JO - Brain Res VL - 843 IS - 1-2 N2 - The precursor of the non-Abeta-component of Alzheimer's disease (AD) amyloid (NACP, alpha-synuclein) aggregates into insoluble filaments of Lewy bodies (LBs) in Parkinson's disease (PD) and dementia with LBs (DLB). The microtubule-associated protein tau is an integral component of filaments of neurofibrillary tangles (NFTs). NFTs are occasionally found in brains of PD and DLB; however, the presence of NFTs or tau-epitopes within LB-containing neurons is rare. Double-immunofluorescence study and peroxidase-immunohistochemical study in serial sections, performed to examine the co-localization of tau- and NACP-epitopes in the brainstem of PD and DLB, demonstrated that four different epitopes of tau including phosphorylation-dependent and independent ones were present in a minority of LBs, but more often than previously considered. A tau (tau2)-epitope was localized to filaments in the outer layers of brainstem-type LBs by immunoelectron microscopy. Therefore, we conclude that tau is incorporated into filaments in certain LBs. Extensive investigation has enabled us to classify this co-localization into four types: type 1, LBs with ring-shaped tau-immunoreactivity; type 2, LBs surrounded by NFTs; type 3, NACP- and tau-immunoreactive filamentous and granular masses; and type 4, NACP- and tau-immunoreactive dystrophic neurites. This study raises a new question whether aggregation and hyperphosphorylation of tau in PD and DLB are triggered by the collapse of intraneuronal organization of microtubules due to NACP-filament aggregation in neuronal perikarya and axons. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/10528110/Cellular_co_localization_of_phosphorylated_tau__and_NACP/alpha_synuclein_epitopes_in_lewy_bodies_in_sporadic_Parkinson's_disease_and_in_dementia_with_Lewy_bodies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(99)01848-X DB - PRIME DP - Unbound Medicine ER -