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

• Published in: Brain research Vol. 843; no. 1; pp. 53 - 61
• Main Authors: Arima, Kunimasa, Hirai, Shigeo, Sunohara, Nobuhiko, Aoto, Kazuko, Izumiyama, Yoko, Uéda, Kenji, Ikeda, Kazuhiko, Kawai, Mitsuru
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 02.10.1999; Amsterdam Elsevier; New York, NY
• Subjects: a-Synuclein; Aged; Aged, 80 and over; alpha-Synuclein; Biological and medical sciences; Brain - metabolism; Brain - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Epitopes - analysis; Female; Filament aggregation; Humans; Immunohistochemistry; Lewy bodies; Lewy Bodies - metabolism; Lewy Bodies - pathology; Lewy body; Lewy Body Disease - metabolism; Lewy Body Disease - pathology; Male; Medical sciences; Middle Aged; NACP; Nerve Tissue Proteins - analysis; Nerve Tissue Proteins - metabolism; Neurology; Neuronal degeneration; Parkinson Disease - metabolism; Parkinson Disease - pathology; Phosphoproteins - analysis; Phosphoproteins - metabolism; Phosphorylation; Synuclein; Synucleins; Tau; tau Proteins - analysis; tau Proteins - metabolism; Neuronal degeneration; Filament aggregation; Tau; NACP; Synuclein; Lewy body; Human; Nervous system diseases; Antigenic determinant; Parkinson disease; Coexistence; Cerebral disorder; Tau protein; Central nervous system disease; Degenerative disease; Localization; Extrapyramidal syndrome
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(99)01848-X

The precursor of the non-Aβ-component of Alzheimer's disease (AD) amyloid (NACP, α-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.