Neurofibrillary tangles in progressive supranuclear palsy brains exhibit immunoreactivity to frameshift mutant ubiquitin-B protein

In Alzheimer's disease (AD) neurofibrillary tangles (NFT) are strongly tau and ubiquitin immunopositive, and contain an aberrant form of ubiquitin der ived from the ubiquitin-B gene denoted as UBB+1. We explored whether the ta u-related NFT seen in another neurodegenerative disease, progressive supran uclear palsy (PSP), also showed an accumulation of UBB+1. Three cases of PS P were examined immunohistochemically for tau protein, ubiquitin-protein co njugates and UBB+1 using single and double labelling. We conclude that UBB1 is associated with compact globose tangles rather than dispersed accumula tions of tau in PSP, showing that its presence is not unique to AD. We prop ose that aggregation of ubiquitinated proteins into compact inclusions in P SP might be due to inhibition of the degradation of multiubiquitinated prot eins by ubiquitin chains containing proximal UBB+1 rather than normal ubiqu itin. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.