Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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

Harvard

Southwell, AL, Smith, SEP, Davis, TR, Caron, NS, Villanueva, EB, Xie, Y, Collins, JA, Ye, ML, Sturrock, A, Leavitt, BR, Schrum, AG & Hayden, MR 2015, 'Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression', Scientific Reports, vol. 5, pp. 12166. https://doi.org/10.1038/srep12166

APA

Southwell, A. L., Smith, S. E. P., Davis, T. R., Caron, N. S., Villanueva, E. B., Xie, Y., Collins, J. A., Ye, M. L., Sturrock, A., Leavitt, B. R., Schrum, A. G., & Hayden, M. R. (2015). Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression. Scientific Reports, 5, 12166. https://doi.org/10.1038/srep12166

Vancouver

Southwell AL, Smith SEP, Davis TR, Caron NS, Villanueva EB, Xie Y et al. Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression. Scientific Reports. 2015 Jul 15;5:12166. https://doi.org/10.1038/srep12166

Author

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. / Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression. In: Scientific Reports. 2015 ; Vol. 5. pp. 12166.

Bibtex

@article{0368b6c385ec4e32b53a6c739148af70,
title = "Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression",
abstract = "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. ",
keywords = "Adult, Aged, Animals, Brain/metabolism, Disease Models, Animal, Female, Flow Cytometry, Humans, Huntingtin Protein, Huntington Disease/metabolism, Immunoblotting, Immunoprecipitation, Male, Mice, Middle Aged, Mutation, Nerve Tissue Proteins/cerebrospinal fluid, Recombinant Fusion Proteins/biosynthesis, Severity of Illness Index",
author = "Southwell, {Amber L} and Smith, {Stephen E P} and Davis, {Tessa R} and Caron, {Nicholas S} and Villanueva, {Erika B} and Yuanyun Xie and Collins, {Jennifer A} and Ye, {Min Li} and Aaron Sturrock and Leavitt, {Blair R} and Schrum, {Adam G} and Hayden, {Michael R}",
year = "2015",
month = jul,
day = "15",
doi = "10.1038/srep12166",
language = "English",
volume = "5",
pages = "12166",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",

}

RIS

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