{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:32:59Z","timestamp":1791268379559,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2002,5,21]],"date-time":"2002-05-21T00:00:00Z","timestamp":1021939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2002,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pick's disease is characterized neuropathologically by distinct \u03c4\u2010immunoreactive intraneuronal inclusions known as Pick bodies and by insoluble \u03c4 proteins with predominantly three microtubule\u2010binding repeat \u03c4 isoforms. However, recent immunohistochemical studies showed that the antibody specific for exon 10, which encodes the fourth microtubule\u2010binding repeat, detected other \u03c4 lesions in Pick's disease. To better define the spectrum of \u03c4 pathology in Pick's disease, we used biochemical, immunohistochemical, and ultrastructural techniques to analyze the \u03c4 isoform composition in 14 Pick's disease brains. Western blot analysis showed that both three and four microtubule\u2010binding repeat pathological \u03c4 isoforms are present in gray and white matter of various brain regions. Using phosphorylation\u2010dependent anti\u2010\u03c4 antibodies, we show that major \u03c4 phosphoepitopes are present in sarcosyl\u2010insoluble 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\u2010binding repeat \u03c4 isoforms are present in Pick bodies from selected brains. Isolated \u03c4 filaments were straight or twisted and formed by three microtubule\u2010binding repeat or four microtubule\u2010binding repeat \u03c4 isoforms. Major \u03c4 phosphorylation\u2013dependent and exon 10\u2013specific 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\u2010binding repeat \u03c4 pathology in both cortical gray and white matter that distinguish this tauopathy from other neurodegenerative disorders.<\/jats:p>","DOI":"10.1002\/ana.10222","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T23:29:46Z","timestamp":1030318186000},"page":"730-739","source":"Crossref","is-referenced-by-count":133,"title":["Sporadic Pick's disease: A tauopathy characterized by a spectrum of pathological \u03c4 isoforms in gray and white 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