| Title: | Unveiling the glymphatic system's role in brain aging: A comprehensive biomarker and modifiable intervention target. |
| Journal: | Proceedings of the National Academy of Sciences of the United States of America |
| Published: | 27 Apr 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42044335/ |
| DOI: | https://doi.org/10.1073/pnas.2516601123 |
Publication 17827
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Abstract
The focus of this study is to investigate the role of diffusion tensor imaging along the perivascular space (DTI-ALPS) index in brain aging. To address this, we first examined the association of DTI-ALPS with aging hallmarks among 40,488 UK Biobank (UKB) participants. Next, we developed normative brain age models incorporating the DTI-ALPS index from 12,401 healthy UKB adults and validated in UKB-ADNI and UKB-TALENT datasets. Finally, we explored the relationship between brain age gap (BAG) with peripheral organ function, chronic diseases, proteomics, and genetics, while identifying modifiable factors in a longitudinal cohort. The findings revealed that DTI-ALPS index correlated with chronological age, telomere length, brain structure, and cognition. A brain age model integrating the DTI-ALPS index achieved good accuracy in the UKB (r = 0.756) and replicated well in two independent datasets (UKB-ADNI: r = 0.766; UKB-TALENT: r = 0.724), with choroid plexus volume emerging as an additional contributor. Musculoskeletal health was a key driver for brain aging in females, while pulmonary metrics prevailed in males. Neurodegenerative and metabolic disorders increased BAGs, imparting increased mortality risk. Protein-wide and genome-wide analysis identified 154 BAG-related proteins and 11 loci. Modifiable factors, particularly systolic blood pressure below 120 mmHg, were strongly associated with reduced BAGs. Overall, the DTI-ALPS index is a promising brain aging biomarker, offering insights into links between brain and peripheral health, and highlighting sex-stratified therapeutic strategies. Aggressive blood pressure control may mitigate brain aging and promote long-term brain health.</p>
14 Keywords
- Adult
- Aged
- Aged, 80 and over
- Aging
- Biomarkers
- Brain
- Cognition
- Diffusion Tensor Imaging
- Female
- Glymphatic System
- Humans
- Longitudinal Studies
- Male
- Middle Aged
17 Authors
- Yuanyuan Fang
- Wenxi Luo
- Hao Huang
- Lusen Ran
- Yuqin He
- Chang Cheng
- Yao Yao
- Yuxiang Hou
- Haibo Zheng
- Dengji Pan
- Shabei Xu
- Xiang Luo
- Tingting Qin
- Xingjie Hao
- Feng Lu
- Wei Wang
- Minghuan Wang
1 Application
| Application ID | Title |
|---|---|
| 90311 | Association of Lifestyle Behaviors and Genetic Risk With cardio-cerebrovascular diseases. |
Enabling scientific discoveries that improve human health