Plasma proteomics identify biomarkers and undulating changes of brain aging

Wei-Shi Liu¹, Jia You², Shi-Dong Chen¹, Yi Zhang¹, Jian-Feng Feng^{2

3}, Yu-Ming Xu^{4

5}, Jin-Tai Yu⁶, Wei Cheng^{7

8

9}

Affiliations

¹ Department 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.
² Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China.
³ Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China.
⁴ Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. xuyuming@zzu.edu.cn.
⁵ NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China. xuyuming@zzu.edu.cn.
⁶ Department 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. jintai_yu@fudan.edu.cn.
⁷ Department 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. wcheng@fudan.edu.cn.
⁸ Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China. wcheng@fudan.edu.cn.
⁹ Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China. wcheng@fudan.edu.cn.

PMID: 39653801
DOI: 10.1038/s43587-024-00753-6

Plasma proteomics identify biomarkers and undulating changes of brain aging

Wei-Shi Liu et al. Nat Aging. 2025 Jan.

. 2025 Jan;5(1):99-112.

doi: 10.1038/s43587-024-00753-6. Epub 2024 Dec 9.

Authors

Wei-Shi Liu¹, Jia You², Shi-Dong Chen¹, Yi Zhang¹, Jian-Feng Feng^{2

3}, Yu-Ming Xu^{4

5}, Jin-Tai Yu⁶, Wei Cheng^{7

8

9}

Affiliations

¹ Department 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.
² Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China.
³ Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China.
⁴ Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. xuyuming@zzu.edu.cn.
⁵ NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China. xuyuming@zzu.edu.cn.
⁶ Department 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. jintai_yu@fudan.edu.cn.
⁷ Department 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. wcheng@fudan.edu.cn.
⁸ Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China. wcheng@fudan.edu.cn.
⁹ Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China. wcheng@fudan.edu.cn.

PMID: 39653801
DOI: 10.1038/s43587-024-00753-6

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.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

1. Cai, Y. et al. The landscape of aging. Sci. China Life Sci. 65, 2354–2454 (2022). - PubMed - PMC - DOI
1. Aging Biomarker Consortium et al. Biomarkers of aging. Sci. China Life Sci. 66, 893–1066 (2023). - PMC - DOI
1. Fratiglioni, L., Marseglia, A. & Dekhtyar, S. Ageing without dementia: can stimulating psychosocial and lifestyle experiences make a difference? Lancet Neurol. 19, 533–543 (2020). - PubMed - DOI
1. Hou, Y. et al. Ageing as a risk factor for neurodegenerative disease. Nat. Rev. Neurol. 15, 565–581 (2019). - PubMed - DOI
1. Mattson, M. P. & Arumugam, T. V. Hallmarks of brain aging: adaptive and pathological modification by metabolic states. Cell Metab. 27, 1176–1199 (2018). - PubMed - PMC - DOI

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Plasma proteomics identify biomarkers and undulating changes of brain aging

Affiliations

Plasma proteomics identify biomarkers and undulating changes of brain aging

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

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LinkOut - more resources

Full Text Sources

Medical

Miscellaneous