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Huntingtin\u2010aggregates are indeed a major hallmark of this disorder and could represent useful markers of disease\u2010onset or progression. We designed a simple method for qualitative and quantitative characterization of aggregates. For this, we analyzed samples from <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> Huntington\u2019s Disease models by agarose gel electrophoresis and showed that in the brain of transgenic mice huntingtin\u2010aggregates became larger as a function of disease progression. This appears to be a property of cytoplasmic but not nuclear aggregates. In cell cultures, treatment with Congo Red inhibited aggregate growth but not total load. Finally, we showed that in primary striatal neurons and in brains of R6\/2 and <jats:italic>Hdh<\/jats:italic>Q150 mice, the presence of aggregates preceded initiation of any other functional deficits. This observation argues for a pathogenic role of huntingtin\u2010aggregation in Huntington\u2019s Disease. Our results emphasize that thorough analysis of huntingtin metabolism and aggregation is now feasible, thus significantly improving the power of studies assessing therapies designed to lower huntingtin levels or to interfere with its aggregation.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2007.05032.x","type":"journal-article","created":{"date-parts":[[2007,10,11]],"date-time":"2007-10-11T20:46:25Z","timestamp":1192135585000},"page":"846-858","source":"Crossref","is-referenced-by-count":101,"title":["Sensitive biochemical aggregate detection reveals aggregation onset before symptom development in cellular and murine models of Huntington\u2019s disease"],"prefix":"10.1111","volume":"104","author":[{"given":"Andreas","family":"Weiss","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Woodman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirupa","family":"Sathasivam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Bibel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"R\u00e9gulier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian P.","family":"Bates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Paganetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,10,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02998"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(06)12003-0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13304-1"},{"key":"e_1_2_7_5_1","volume-title":"Huntington\u2019s Disease","author":"Bates G. 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