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

Abstract

Recent studies have shown the co-existence of alpha-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 alpha-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 alpha-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 alpha-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 alpha-synuclein and UBB+1 was found in only a few neurons. These findings indicate that alpha-synuclein and phosphorylated tau co-occur in certain brain regions in cases of combined MSA and AD and that the proteasomal pathways differ between alpha-synuclein- and pTau-bearing neurons.

• Authors: Beatrice Terni, María Jesús Rey, Susana Boluda, Benjamín Torrejón-Escribano, M Pujol Sabate, Matil Calopa, Fred W van Leeuwen, Isidro Ferrer
• Journal: Acta neuropathologica (Acta Neuropathol) Vol. 113 Issue 4 Pg. 403-16 (Apr 2007) ISSN: 0001-6322 [Print] Germany
• PMID: 17237936 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• SQSTM1 protein, human
• Sequestosome-1 Protein
• UBB protein, human
• Ubiquitin
• alpha-Synuclein
• tau Proteins

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Aged
• Alzheimer Disease (complications, metabolism, pathology)
• Humans
• Male
• Multiple System Atrophy (complications, metabolism, pathology)
• Neurofibrillary Tangles (metabolism)
• Sequestosome-1 Protein
• Ubiquitin (genetics, metabolism)
• alpha-Synuclein (metabolism)
• tau Proteins (metabolism)