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. doi: 10.1016/s0006-8993(99)01848-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Brain / metabolism
  • Brain / pathology*
  • Epitopes / analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Lewy Bodies / metabolism*
  • Lewy Bodies / pathology
  • Lewy Body Disease / metabolism*
  • Lewy Body Disease / pathology
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / metabolism*
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Phosphoproteins / analysis
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Synucleins
  • alpha-Synuclein
  • tau Proteins / analysis
  • tau Proteins / metabolism*

Substances

  • Epitopes
  • Nerve Tissue Proteins
  • Phosphoproteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein
  • tau Proteins