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.
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.
Arima
K
K
Department of Ultrastructure and Histochemistry, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo, Japan. arima@prit.go.jp
Hirai
S
S
Sunohara
N
N
Aoto
K
K
Izumiyama
Y
Y
Uéda
K
K
Ikeda
K
K
Kawai
M
M
D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D000939:Epitopes / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000378:metabolism* / Q000473:pathology; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D010766:Phosphorylation; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism*
D000939:Epitopes; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins