Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression
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Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression. / Southwell, Amber L; Smith, Stephen E P; Davis, Tessa R; Caron, Nicholas S; Villanueva, Erika B; Xie, Yuanyun; Collins, Jennifer A; Ye, Min Li; Sturrock, Aaron; Leavitt, Blair R; Schrum, Adam G; Hayden, Michael R.
In: Scientific Reports, Vol. 5, 15.07.2015, p. 12166.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression
AU - Southwell, Amber L
AU - Smith, Stephen E P
AU - Davis, Tessa R
AU - Caron, Nicholas S
AU - Villanueva, Erika B
AU - Xie, Yuanyun
AU - Collins, Jennifer A
AU - Ye, Min Li
AU - Sturrock, Aaron
AU - Leavitt, Blair R
AU - Schrum, Adam G
AU - Hayden, Michael R
PY - 2015/7/15
Y1 - 2015/7/15
N2 - Quantitation of huntingtin protein in the brain is needed, both as a marker of Huntington disease (HD) progression and for use in clinical gene silencing trials. Measurement of huntingtin in cerebrospinal fluid could be a biomarker of brain huntingtin, but traditional protein quantitation methods have failed to detect huntingtin in cerebrospinal fluid. Using micro-bead based immunoprecipitation and flow cytometry (IP-FCM), we have developed a highly sensitive mutant huntingtin detection assay. The sensitivity of huntingtin IP-FCM enables accurate detection of mutant huntingtin protein in the cerebrospinal fluid of HD patients and model mice, demonstrating that mutant huntingtin levels in cerebrospinal fluid reflect brain levels, increasing with disease stage and decreasing following brain huntingtin suppression. This technique has potential applications as a research tool and as a clinical biomarker.
AB - Quantitation of huntingtin protein in the brain is needed, both as a marker of Huntington disease (HD) progression and for use in clinical gene silencing trials. Measurement of huntingtin in cerebrospinal fluid could be a biomarker of brain huntingtin, but traditional protein quantitation methods have failed to detect huntingtin in cerebrospinal fluid. Using micro-bead based immunoprecipitation and flow cytometry (IP-FCM), we have developed a highly sensitive mutant huntingtin detection assay. The sensitivity of huntingtin IP-FCM enables accurate detection of mutant huntingtin protein in the cerebrospinal fluid of HD patients and model mice, demonstrating that mutant huntingtin levels in cerebrospinal fluid reflect brain levels, increasing with disease stage and decreasing following brain huntingtin suppression. This technique has potential applications as a research tool and as a clinical biomarker.
KW - Adult
KW - Aged
KW - Animals
KW - Brain/metabolism
KW - Disease Models, Animal
KW - Female
KW - Flow Cytometry
KW - Humans
KW - Huntingtin Protein
KW - Huntington Disease/metabolism
KW - Immunoblotting
KW - Immunoprecipitation
KW - Male
KW - Mice
KW - Middle Aged
KW - Mutation
KW - Nerve Tissue Proteins/cerebrospinal fluid
KW - Recombinant Fusion Proteins/biosynthesis
KW - Severity of Illness Index
U2 - 10.1038/srep12166
DO - 10.1038/srep12166
M3 - Journal article
C2 - 26174131
VL - 5
SP - 12166
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
ER -
ID: 236603322