Evidence map›Paper›PMID 39885106›Full record

ArticleMolecular neurobiology2025

Prospective Investigation Unravels Plasma Proteomic Links to Dementia.

Jincheng Li, Jialin Li, Shuaizhou Chen, Zhenqiu Liu, Jiacheng Dai, Yingzhe Wang, Mei Cui, Chen Suo, Kelin Xu, Li Jin and 2 more

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Journal of the American Heart Association · 2026
    Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Jincheng Li *Research and Innovation Center, Shanghai Pudong Hospital, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, 200433, China.
Jialin Li *Research and Innovation Center, Shanghai Pudong Hospital, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, 200433, China.
Shuaizhou ChenResearch and Innovation Center, Shanghai Pudong Hospital, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, 200433, China.
Zhenqiu LiuResearch and Innovation Center, Shanghai Pudong Hospital, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, 200433, China.
Jiacheng DaiResearch and Innovation Center, Shanghai Pudong Hospital, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, 200433, China.
Yingzhe WangDepartment of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Mei CuiDepartment of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Chen SuoFudan University Taizhou Institute of Health Sciences, Taizhou, 225300, Jiangsu, China.
Kelin XuFudan University Taizhou Institute of Health Sciences, Taizhou, 225300, Jiangsu, China.
Li JinFudan University Taizhou Institute of Health Sciences, Taizhou, 225300, Jiangsu, China.
Xingdong ChenFudan University Taizhou Institute of Health Sciences, Taizhou, 225300, Jiangsu, China. xingdongchen@fudan.edu.cn.
Yanfeng JiangResearch and Innovation Center, Shanghai Pudong Hospital, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, 200433, China. yanfengjiang@fudan.edu.cn.

Funding

Key Research and Development Plans of Jiangsu Province, China BE2021696National Key Research and Development program of China 2022YFC3400700National Key Research and Development Program of China 2021YFC2500100Natural Science Foundation of Shanghai, China 22ZR1405300Science and Technology Innovation 2030 Major Projects 2021ZD0201806Science and Technology Innovation 2030 Major Projects 2022ZD0211600Shanghai Rising-Star Program 22QA1404000
6 · The paper itself

Abstract

Investigating plasma proteomic signatures of dementia offers insights into its pathology, aids biomarker discovery, supports disease monitoring, and informs drug development. Here, we analyzed data from 48,367 UK Biobank participants with proteomic profiling. Using Cox and generalized linear models, we examined the longitudinal associations between proteomic signatures and dementia-related phenotypes. Mendelian randomization analysis was employed to identify causal associations, and machine learning algorithms were applied to develop protein-based models for dementia prediction. We identified 74 proteins significantly associated with the risk of various types of dementia and cognitive functions after Bonferroni correction. Among these, strong associations were observed for growth/differentiation factor 15 (GDF15), glial fibrillary acidic protein (GFAP), and neurofilament light polypeptide (NEFL), across all types of dementia. Additionally, 15 proteins demonstrated significant associations with neuroimaging-defined dementia endophenotypes. Two-sample Mendelian randomization analyses further substantiated causal relationships between dementia-associated proteins and Alzheimer's disease, particularly involving GDF15, proto-oncogene tyrosine-protein kinase receptor Ret (RET), and GFAP. Moreover, we identified three protein modules associated with dementia, primarily linked to immune system processes, angiogenesis, and energy metabolism, providing insights into potential biological pathways underlying the disease. Furthermore, we proposed a ten-protein panel capable of forecasting dementia over a median follow-up period of 8.6 years, achieving an area under the curve (AUC) of 0.857 (95% confidence interval (CI), 0.837-0.876). Our results revealed dementia-associated plasma proteomic signatures, and their causal relationships, notably GDF15-RET signaling with Alzheimer's disease, and proposed a promising protein panel for high-risk dementia screening.

Indexed as

DementiaProteomicsAgedBiomarkersFemaleHumansMaleMendelian Randomization AnalysisProspective StudiesProto-Oncogene MasBiomarkersMAS1 protein, humanProto-Oncogene MasBiomarkerCausal relationshipDementiaEarly detectionPlasma proteomic

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.