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Mutant ubiquitin and p62 immunoreactivity in cases of combined multiple system atrophy and Alzheimer’s disease

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Abstract

Recent studies have shown the co-existence of α-synuclein and phosphorylated tau (pTau) in several neurodegenerative diseases. Here, we report two autopsy cases of combined multiple system atrophy (MSA) and Alzheimer’s disease (AD). In both cases, abundant α-synuclein-positive glial and neuronal cytoplasmic inclusions were found in the brainstem, amygdala and hippocampal formation. pTau-positive neurofibrillary tangles (NFTs) were widely distributed in case 1 (Braak stage VI) and moderate in case 2 (Braak stage III). Although α-synuclein and pTau pathology co-occurred in the hippocampus and entorhinal cortex, only a few neurons showed co-existence of these two proteins. Immunoreactivity for p62, a ubiquitin proteasome system related protein, was found in the majority of NFTs, but in only a small proportion of neuronal α-synuclein inclusions. In addition, UBB+1, a mutant form of ubiquitin and a marker for proteasomal dysfunction, was present in the majority of NFTs, whereas co-existence of α-synuclein and UBB+1 was found in only a few neurons. These findings indicate that α-synuclein and phosphorylated tau co-occur in certain brain regions in cases of combined MSA and AD and that the proteasomal pathways differ between α-synuclein- and pTau-bearing neurons.

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Acknowledgments

BT is the recipient of a Beatriu de Pinós grant from the Generalitat de Catalunya. This work was funded by grants from the Spanish Ministry of Health, Instituto de Salud Carlos III (PI05/1570), and supported by the European Commission under the Sixth Framework Programme (BrainNet Europe II, LSHM-CT-2004-503039). FWVL is grateful for the support of the Jan Dekker and Ludgardine Bouwman funds, Matty Brand Stichting and the Society for PSP (grant #440-04). We wish to thank T. Yohannan for the editorial assistance.

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Authors and Affiliations

  1. Institut de Neuropatologia, Servei Anatomia Patològica, Facultad de Medicina, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Hospitalet de Llobregat, Carrer Feixa Llarga sn, 08907 Hospitalet de Llobregat, Barcelona, Spain

    Beatrice Terni, Susana Boluda & Isidro Ferrer

  2. Banc de Teixits Neurològics Universitat de Barcelona-Hospital Clinic, Barcelona, Spain

    María Jesús Rey & Isidro Ferrer

  3. Serveis Científico-Tècnics, Unitat de Biología de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain

    Benjamín Torrejón-Escribano

  4. Servei de Neurologia, Hospital Santa María, Lleida, Spain

    M. Pujol Sabate

  5. Servei de Neurologia, Hospital Universitari de Bellvitge, Barcelona, Spain

    Matil Calopa

  6. Department of Psychiatry and Neuropsychology, Division of Cellular Neuroscience, Maastricht, The Netherlands

    Fred W. van Leeuwen

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  1. Beatrice Terni
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Terni, B., Rey, M.J., Boluda, S. et al. Mutant ubiquitin and p62 immunoreactivity in cases of combined multiple system atrophy and Alzheimer’s disease. Acta Neuropathol 113, 403–416 (2007). https://doi.org/10.1007/s00401-006-0192-3

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  • DOI: https://doi.org/10.1007/s00401-006-0192-3

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