title: 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.affiliation: 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.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Terni
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Rey
authors.forename: Susana
authors.initials: S
authors.lastname: Boluda
authors.forename: Benjamín
authors.initials: B
authors.lastname: Torrejón-Escribano
authors.forename: M Pujol
authors.initials: MP
authors.lastname: Sabate
authors.forename: Matil
authors.initials: M
authors.lastname: Calopa
authors.forename: Fred W
authors.initials: FW
authors.lastname: van Leeuwen
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D019578:Multiple System Atrophy / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C479419:UBB protein, human; D025801:Ubiquitin; D051844:alpha-Synuclein; D016875:tau Proteins