TY - JOUR
T1 - Blood-Based Proteomics for Adult-Onset Focal Dystonias
AU - Timsina, Jigyasha
AU - Dinasarapu, Ashok
AU - Kilic-Berkmen, Gamze
AU - Budde, John
AU - Sung, Yun Ju
AU - Klein, Adam M.
AU - Cruchaga, Carlos
AU - Jinnah, H. A.
N1 - Publisher Copyright:
© 2024 American Neurological Association.
PY - 2024/7
Y1 - 2024/7
N2 - Objectives: The adult-onset focal dystonias are characterized by over-active muscles leading to abnormal movements. For most cases, the etiology and pathogenesis remain unknown. In the current study, unbiased proteomics methods were used to identify potential changes in blood plasma proteins. Methods: A large-scale unbiased proteomics screen was used to compare proteins (N = 6,345) in blood plasma of normal healthy controls (N = 49) with adult-onset focal dystonia (N = 143) consisting of specific subpopulations of cervical dystonia (N = 45), laryngeal dystonia (N = 49), and blepharospasm (N = 49). Pathway analyses were conducted to identify relevant biological pathways. Finally, protein changes were used to build a prediction model for dystonia. Results: After correction for multiple comparisons, 15 proteins were associated with adult-onset focal dystonia. Subgroup analyses revealed some proteins were shared across the dystonia subgroups while others were unique to 1 subgroup. The top biological pathways involved changes in the immune system, metal ion transport, and reactive oxygen species. A 4-protein model showed high accuracy in discriminating control individuals from dystonia cases [average area under the curve (AUC) = 0.89]. Interpretation: These studies provide novel insights into the etiopathogenesis of dystonia, as well as novel potential biomarkers. ANN NEUROL 2024;96:110–120.
AB - Objectives: The adult-onset focal dystonias are characterized by over-active muscles leading to abnormal movements. For most cases, the etiology and pathogenesis remain unknown. In the current study, unbiased proteomics methods were used to identify potential changes in blood plasma proteins. Methods: A large-scale unbiased proteomics screen was used to compare proteins (N = 6,345) in blood plasma of normal healthy controls (N = 49) with adult-onset focal dystonia (N = 143) consisting of specific subpopulations of cervical dystonia (N = 45), laryngeal dystonia (N = 49), and blepharospasm (N = 49). Pathway analyses were conducted to identify relevant biological pathways. Finally, protein changes were used to build a prediction model for dystonia. Results: After correction for multiple comparisons, 15 proteins were associated with adult-onset focal dystonia. Subgroup analyses revealed some proteins were shared across the dystonia subgroups while others were unique to 1 subgroup. The top biological pathways involved changes in the immune system, metal ion transport, and reactive oxygen species. A 4-protein model showed high accuracy in discriminating control individuals from dystonia cases [average area under the curve (AUC) = 0.89]. Interpretation: These studies provide novel insights into the etiopathogenesis of dystonia, as well as novel potential biomarkers. ANN NEUROL 2024;96:110–120.
UR - http://www.scopus.com/inward/record.url?scp=85189705690&partnerID=8YFLogxK
U2 - 10.1002/ana.26929
DO - 10.1002/ana.26929
M3 - Article
C2 - 38578115
AN - SCOPUS:85189705690
SN - 0364-5134
VL - 96
SP - 110
EP - 120
JO - Annals of neurology
JF - Annals of neurology
IS - 1
ER -