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A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
Plasma proteomics identify biomarkers and undulating changes of brain aging
Wei-Shi Liu1, Jia You2, Shi-Dong Chen1
1Department of Neurology and National Center for Neurological diseases, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
Abstract:
Proteomics enables the characterization of brain aging biomarkers and discernment of changes during brain aging. We leveraged multimodal brain imaging data from 10,949 healthy adults to estimate brain age gap (BAG), an indicator of brain aging. Proteome-wide association analysis across 4,696 participants of 2,922 proteins identified 13 significantly associated with BAG, implicating stress, regeneration and inflammation. Brevican (BCAN) (β = -0.838, P = 2.63 × 10-10) and growth differentiation factor 15 (β = 0.825, P = 3.48 × 10-11) showed the most significant, and multiple, associations with dementia, stroke and movement functions. Dysregulation of BCAN affected multiple cortical and subcortical structures. Mendelian randomization supported the causal association between BCAN and BAG. We revealed undulating changes in the plasma proteome across brain aging, and profiled brain age-related change peaks at 57, 70 and 78 years, implicating distinct biological pathways during brain aging. Our findings revealed the plasma proteomic landscape of brain aging and pinpointed biomarkers for brain disorders.
