Plasma proteomic profiles predict future dementia in healthy adults
Yu Guo1, Jia You1,2, Yi Zhang1
1Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
Nature Aging
|February 12, 2024
Summary
Proteomics can predict dementia. Glial fibrillary acidic protein (GFAP) and other proteins in blood plasma show high accuracy in predicting dementia onset, even over 10 years in advance.
Area of Science:
- Biomarkers and Diagnostics
- Neurodegenerative Diseases
- Proteomics
Background:
- Dementia onset prediction remains a significant challenge in clinical practice.
- Proteomic analysis offers a novel avenue for identifying predictive biomarkers.
- Early detection of dementia is crucial for timely intervention and management.
Purpose of the Study:
- To investigate the utility of plasma proteins for predicting incident dementia.
- To identify specific proteins associated with all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VaD).
- To evaluate the predictive performance of identified proteins, alone and in combination with demographics.
Main Methods:
- Analysis of plasma protein data from 52,645 UK Biobank participants without dementia.
- Longitudinal follow-up for incident dementia cases (1,417) over 14.1 years.
- Statistical association and importance ordering of 1,463 plasma proteins.
Main Results:
- GFAP, NEFL, GDF15, and LTBP2 were consistently associated with incident ACD, AD, and VaD.
- Combining GFAP or GDF15 with demographics yielded high prediction accuracy (AUC 0.872–0.912).
- Elevated GFAP levels increased dementia likelihood by 2.32 times; GFAP and NEFL changed >10 years pre-diagnosis.
Conclusions:
- Plasma proteomics, particularly GFAP, demonstrates strong potential as an early biomarker for dementia prediction.
- GFAP and LTBP2 show high specificity for dementia prediction.
- These findings support GFAP's role in early dementia screening and risk stratification.
