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.
Nature Aging
|December 9, 2024
Summary
This study identified key plasma proteins linked to brain aging, including Brevican (BCAN), offering new biomarkers for brain health and disorders.
Area of Science:
- Neuroscience
- Proteomics
- Aging Research
Background:
- Brain aging involves complex molecular changes.
- Identifying reliable biomarkers for brain aging is crucial for understanding and managing age-related neurological disorders.
- Proteomics offers a powerful lens to study these changes at a molecular level.
Purpose of the Study:
- To characterize brain aging biomarkers using proteomics.
- To identify proteins associated with brain age gap (BAG) in healthy adults.
- To explore the role of specific proteins in neurological functions and disorders.
Main Methods:
- Leveraged multimodal brain imaging data from 10,949 healthy adults to calculate brain age gap (BAG).
- Conducted a proteome-wide association analysis of 2,922 proteins in 4,696 participants.
- Utilized Mendelian randomization to investigate causal associations between identified proteins and BAG.
Main Results:
- Identified 13 proteins significantly associated with BAG, implicating stress, regeneration, and inflammation pathways.
- Brevican (BCAN) and growth differentiation factor 15 (GDF15) showed the strongest associations with BAG and neurological functions.
- BCAN dysregulation impacted multiple brain structures, and Mendelian randomization supported its causal link to BAG.
- Revealed age-related proteomic changes with peaks at 57, 70, and 78 years, highlighting distinct biological pathways.
Conclusions:
- The plasma proteomic landscape of brain aging was profiled.
- Identified BCAN and GDF15 as significant biomarkers for brain aging and associated neurological functions.
- Findings provide novel insights into the molecular mechanisms of brain aging and potential targets for brain disorder interventions.
