Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies

We examined the immunoreactivity of ubiquitin-binding protein p62 and its a ssociation with ubiquitin (Ub), alpha -synuclein, and paired helical filame nt (PHF)-tau in the affected brain areas of human tauopathies and synuclein opathies. Ubiquitin-binding protein p62 is a widely expressed protein that can bind to Ub noncovalently and is involved in several signalling pathways . making p62 a candidate regulator of Ub-mediated proteolysis. We show that p62 immunoreactivity co-localizes with neuronal and glial Ub-containing in clusions in Alzheimer's disease, Pick's disease, dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy. This is the first demons tration of a common protein component, apart from Ub, that is present in bo th PHF-tau and alpha -synuclein inclusions. In both tauo- and synucleinopat hies, the staining patterns for p62 and Ub were markedly similar, suggestin g that a common mechanism which requires interaction of p62 and Ub contribu tes to the formation of PHF-tau and alpha -synuclein inclusions. NeuroRepor t 12:2085-2090 (C) 2001 Lippincott Williams & Wilkins.