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.

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.

journal_name

Brain Res

journal_title

Brain research

authors

Arima K,Hirai S,Sunohara N,Aoto K,Izumiyama Y,Uéda K,Ikeda K,Kawai M

doi

10.1016/s0006-8993(99)01848-x

subject

Has Abstract

pub_date

1999-10-02 00:00:00

pages

53-61

issue

1-2

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(99)01848-X

journal_volume

843

pub_type

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