Sporadic Pick's disease: A tauopathy characterized by a spectrum of pathological τ isoforms in gray and white matter

Victoria Zhukareva, David Mann, Stuart Pickering-Brown, Kunihiro Uryu, Theresa Shuck, Keyur Shah, Murray Grossman, Bruce L. Miller, Christine M. Hulette, Stuart C. Feinstein, John Q. Trojanowski, Virginia M Y Lee

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Pick's disease is characterized neuropathologically by distinct τ-immunoreactive intraneuronal inclusions known as Pick bodies and by insoluble τ proteins with predominantly three microtubule-binding repeat τ isoforms. However, recent immunohistochemical studies showed that the antibody specific for exon 10, which encodes the fourth microtubule-binding repeat, detected other τ lesions in Pick's disease. To better define the spectrum of τ pathology in Pick's disease, we used biochemical, immunohistochemical, and ultrastructural techniques to analyze the τ isoform composition in 14 Pick's disease brains. Western blot analysis showed that both three and four microtubule-binding repeat pathological τ isoforms are present in gray and white matter of various brain regions. Using phosphorylation-dependent anti-τ anti-bodies, we show that major τ phosphoepitopes are present in sarcosyl-insoluble gray and white matter regions of Pick's disease brains. Also, for the first time to our knowledge, we demonstrated that isoforms with four microtubule-binding repeat τ isoforms are present in Pick bodies from selected brains. Isolated τ filaments were straight or twisted and formed by three microtubule-binding repeat or four microtubule-binding repeat τ isoforms. Major τ phosphorylation-dependent and exon 10-specific epitopes were present in filaments. Therefore, Pick's disease is characterized by an accumulations of Pick bodies in the hippocampal region and cortex as well as the presence of three and four microtubule-binding repeat τ pathology in both cortical gray and white matter that distinguish this tauopathy from other neurodegenerative disorders.
    Original languageEnglish
    Pages (from-to)730-739
    Number of pages9
    JournalAnnals of Neurology
    Volume51
    Issue number6
    DOIs
    Publication statusPublished - 2002

    Keywords

    • Aged
    • Aged, 80 and over
    • Blotting, Western
    • Brain Chemistry
    • metabolism: Cerebral Cortex
    • Female
    • metabolism: Hippocampus
    • Humans
    • Male
    • Middle Aged
    • metabolism: Pick Disease of the Brain
    • Protein Isoforms
    • Research Support, Non-U.S. Gov't
    • Research Support, U.S. Gov't, P.H.S.
    • metabolism: Tauopathies
    • chemistry: tau Proteins

    Research Beacons, Institutes and Platforms

    • Dementia@Manchester

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