Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in Lewy bodies in sporadic Parkinson's disease and in dementia withLewy bodies

The precursor of the non-A beta-component of Alzheimer's disease (AD) amylo id (NACP, alpha-synuclein) aggregates into insoluble filaments of Lewy bodi es (LBs) in Parkinson's disease (PD) and dementia with LBs (DLB). The micro tubule-associated protein tan is an integral component of filaments of neur ofibrillary tangles (NFTs). NFTs are occasionally found in brains of PD and DLB; however, the presence of NFTs or tau-epitopes within LB-containing ne urons is rare. Double-immunofluorescence study and peroxidase-immunohistoch emical study in serial sections, performed to examine the co-localization o f tau- and NACP-epitopes in the brainstem of PD and DLB, demonstrated that four different epitopes of tau including phosphorylation-dependent and inde pendent ones were present in a minority of LBs, but more often than previou sly considered. A tau (tau2)-epitope was localized to filaments in the oute r 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 typ es: type 1, LBs with ring-shaped tau-immunoreactivity; type 2, LBs surround ed by NFTs; type 3, NACP- and tau-immunoreactive filamentous and granular m asses; and type 4, NACP- and tau-immunoreactive dystrophic neurites. This s tudy raises a new question whether aggregation and hyperphosphorlation of t au in PD and DLB are triggered by the collapse of intraneuronal organizatio n of microtubules due to NACP-filament aggregation in neuronal perikarya an d axons, (C) 1999 Elsevier Science B.V. All rights reserved.