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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.

  [ 1 vote ]   [ Discuss This Article ]
By Arima K, Hirai S, Sunohara N, Aoto K, Izumiyama Y, • • October 2, 1999

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.

Source: Brain Res 1999 Oct 2;843(1-2):53-61
PMID: 10528110

(Department of Ultrastructure and Histochemistry, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo, Japan)

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