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01-04-2007 | Original Paper

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

Authors: Beatrice Terni, María Jesús Rey, Susana Boluda, Benjamín Torrejón-Escribano, M. Pujol Sabate, Matil Calopa, Fred W. van Leeuwen, Isidro Ferrer

Published in: Acta Neuropathologica | Issue 4/2007

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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Title: Mutant ubiquitin and p62 immunoreactivity in cases of combined multiple system atrophy and Alzheimer’s disease
Authors: Beatrice Terni
María Jesús Rey
Susana Boluda
Benjamín Torrejón-Escribano
M. Pujol Sabate
Matil Calopa
Fred W. van Leeuwen
Isidro Ferrer
Publication date: 01-04-2007
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 4/2007
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-006-0192-3

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

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