eprintid: 1354397 rev_number: 60 eprint_status: archive userid: 608 dir: disk0/01/35/43/97 datestamp: 2012-08-01 18:36:59 lastmod: 2021-09-18 21:48:13 status_changed: 2012-08-01 18:36:59 type: article metadata_visibility: show item_issues_count: 0 creators_name: Weiss, A creators_name: Träger, U creators_name: Wild, EJ creators_name: Grueninger, S creators_name: Farmer, R creators_name: Landles, C creators_name: Scahill, RI creators_name: Lahiri, N creators_name: Haider, S creators_name: Macdonald, D creators_name: Frost, C creators_name: Bates, GP creators_name: Bilbe, G creators_name: Kuhn, R creators_name: Andre, R creators_name: Tabrizi, SJ title: Mutant huntingtin fragmentation in immune cells tracks Huntington's disease progression ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F77 divisions: F86 keywords: Atrophy, B-Lymphocytes, Biological Markers, Blotting, Western, Caudate Nucleus, Disease Progression, Fluorescence Resonance Energy Transfer, Humans, Huntington Disease, Immunoprecipitation, Leukocytes, Monocytes, Mutation, Nerve Tissue Proteins, T-Lymphocytes note: PMCID: PMC3461928 abstract: Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder caused by an expanded CAG repeat in the gene encoding huntingtin (HTT). Therapeutic approaches to lower mutant HTT (mHTT) levels are expected to proceed to human trials, but noninvasive quantification of mHTT is not currently possible. The importance of the peripheral immune system in neurodegenerative disease is becoming increasingly recognized. Peripheral immune cells have been implicated in HD pathogenesis, but HTT levels in these cells have not been quantified before. A recently described time-resolved Förster resonance energy transfer (TR-FRET) immunoassay was used to quantify mutant and total HTT protein levels in leukocytes from patients with HD. Mean mHTT levels in monocytes, T cells, and B cells differed significantly between patients with HD and controls and between pre-manifest mutation carriers and those with clinical onset. Monocyte and T cell mHTT levels were significantly associated with disease burden scores and caudate atrophy rates in patients with HD. mHTT N-terminal fragments detected in HD PBMCs may explain the progressive increase in mHTT levels in these cells. These findings indicate that quantification of mHTT in peripheral immune cells by TR-FRET holds significant promise as a noninvasive disease biomarker. date: 2012-10-01 official_url: http://dx.doi.org/10.1172/JCI64565 vfaculties: VFBRS oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Journal Article, Research Support, Non-U.S. Gov't verified: verified_manual elements_source: PubMed elements_id: 424516 doi: 10.1172/JCI64565 pii: 64565 lyricists_name: Andre, Ralph lyricists_name: Bates, Gillian lyricists_name: Haider, Salman lyricists_name: Lahiri, Nayana lyricists_name: Landles, Christian lyricists_name: Scahill, Rachael lyricists_name: Tabrizi, Sarah lyricists_name: Traeger, Ulrike lyricists_name: Wild, Edward lyricists_id: RANDR07 lyricists_id: GBATE91 lyricists_id: SHAID10 lyricists_id: NLAHI34 lyricists_id: CLAND22 lyricists_id: RSCAH26 lyricists_id: SJTAB21 lyricists_id: USCHU63 lyricists_id: EJWIL36 full_text_status: public publication: Journal of Clinical Investigation volume: 122 number: 10 pagerange: 3731 - 3736 event_location: United States issn: 0021-9738 citation: Weiss, A; Träger, U; Wild, EJ; Grueninger, S; Farmer, R; Landles, C; Scahill, RI; ... Tabrizi, SJ; + view all <#> Weiss, A; Träger, U; Wild, EJ; Grueninger, S; Farmer, R; Landles, C; Scahill, RI; Lahiri, N; Haider, S; Macdonald, D; Frost, C; Bates, GP; Bilbe, G; Kuhn, R; Andre, R; Tabrizi, SJ; - view fewer <#> (2012) Mutant huntingtin fragmentation in immune cells tracks Huntington's disease progression. Journal of Clinical Investigation , 122 (10) 3731 - 3736. 10.1172/JCI64565 <https://doi.org/10.1172/JCI64565>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1354397/1/JCI64565.pdf