Evidence map›Paper›PMID 41582318›Full record

Observational studyMedicine and science in sports and exercise2026

Plasma Proteomic Signatures of Physical Activity Provide Insights into Biological Impacts and its Protective Role against Dementia.

Gayatri Arani, Amit Arora, Shuai Yang, Jingyue Wu, Jennifer N Kraszewski, Amy Martins, Alexandra Miller, Zebunnesa Zeba, Ayan Jafri, Chengcheng Hu and 14 more

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Medicine and science in sports and exercise, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Gayatri AraniDepartment of Epidemiology and Biostatistics, College of Public Health, University of Arizona, Tucson, AZ.
Amit AroraDepartment of Epidemiology and Biostatistics, College of Public Health, University of Arizona, Tucson, AZ.
Shuai YangDepartment of Epidemiology and Biostatistics, College of Public Health, University of Arizona, Tucson, AZ.
Jingyue WuDepartment of Epidemiology and Biostatistics, College of Public Health, University of Arizona, Tucson, AZ.
Jennifer N KraszewskiDepartment of Epidemiology and Biostatistics, College of Public Health, University of Arizona, Tucson, AZ.
Amy MartinsDepartment of Epidemiology and Biostatistics, College of Public Health, University of Arizona, Tucson, AZ.
Alexandra MillerDepartment of Epidemiology and Biostatistics, College of Public Health, University of Arizona, Tucson, AZ.
Zebunnesa ZebaDivision of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN.
Ayan JafriDepartment of Epidemiology and Biostatistics, College of Public Health, University of Arizona, Tucson, AZ.
Chengcheng HuDepartment of Epidemiology and Biostatistics, College of Public Health, University of Arizona, Tucson, AZ.
Leslie V FarlandDepartment of Epidemiology and Biostatistics, College of Public Health, University of Arizona, Tucson, AZ.
Jennifer W BeaDepartment of Health Promotion Sciences, University of Arizona, Tucson, AZ.
Dawn K ColettaDepartment of Physiology, University of Arizona, Tucson, AZ.
Daniel H AslanDepartment of Anthropology, University of Southern California, Los Angeles, CA.
M Katherine SayreDepartment of Anthropology, University of Southern California, Los Angeles, CA.
Pradyumna K BharadwajDepartment of Psychology, University of Arizona, Tucson, AZ.
Madeline AllyDepartment of Psychology, University of Arizona, Tucson, AZ.
Silvio MaltagliatiDepartment of Anthropology, University of Southern California, Los Angeles, CA.
Mark H C LaiDepartment of Anthropology, University of Southern California, Los Angeles, CA.
Rand WilcoxDepartment of Psychology, University of Southern California, Los Angeles, CA.
Eco DE GeusDepartment of Biological Psychology, Vrije Universiteit, Amsterdam, THE NETHERLANDS.
Gene E AlexanderDepartment of Psychology, University of Arizona, Tucson, AZ.
David A RaichlenDepartment of Anthropology, University of Southern California, Los Angeles, CA.
Yann C KlimentidisDepartment of Epidemiology and Biostatistics, College of Public Health, University of Arizona, Tucson, AZ.

Funding

Inactivity, sedentary behavior, and the risk for Alzheimer’s disease in middle aged to older adultsR01AG072445 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GENE E ALEXANDER, Yann Charles Klimentidis · 2022 to 2026
$3.3M
NIA NIH HHS R01 AG072445UK Biobank 21259
6 · The paper itself

Abstract

purposePhysical activity (PA) and sedentary behavior (SB) are associated with many diseases, including Alzheimer disease and all-cause dementia. However, the specific biological mechanisms through which PA protects against disease are not entirely understood. This study aims to address this gap, with a specific focus on all-cause dementia.

methodsWe first assessed the conventional observational associations of three self-reported and three device-based PA/SB measures with circulating levels of 2911 plasma proteins measured in the UK Biobank ( nmax = 39,160) and assessed functional enrichment of identified proteins. We then used bidirectional Mendelian randomization to further evaluate the evidence for causal relationships of PA/SB with protein levels. Finally, we performed mediation analyses to identify proteins that may mediate the relationship of PA with incident all-cause dementia.

resultsOur findings revealed 41 proteins consistently associated with all PA measures and 1027 proteins associated with at least one PA measure. Both conventional observational and Mendelian randomization study designs converged on proteins that appear to increase as a result of PA, including integrins such as ITGAV and ITGAM, as well as MXRA8, CLEC4A, CLEC4M, LPL, and ADGRG2; and on proteins that appear to decrease as a result of PA such as LEP, INHBC, CLMP, PTGDS, ADM, OGN, and PI3; and on proteins that are more responsive to high-intensity PA, such as CA14, CA6, CA4, KIT, and ANGPT2. Functional enrichment analyses revealed processes such as cell-matrix adhesion, integrin-mediated signaling, and collagen binding. Finally, GDF15, ITGAV, ITGAM, ITGA11, HPGDS, GFAP, ADM, AHNAK, and DPP4 were among 21 unique proteins found to mediate the relationship of PA with all-cause dementia, implicating processes such as synaptic plasticity, neurogenesis, and inflammation.

conclusionsOur results provide insights into how PA affects biological processes and protects against dementia, and provide avenues for future research into the health-promoting effects of PA.

Indexed as

Blood ProteinsDementiaExerciseProteomicsSedentary BehaviorAgedBiomarkersFemaleHumansMaleMendelian Randomization AnalysisUK BiobankBiomarkersBlood ProteinsBIOMARKERSDEMENTIAEXERCISEMEDIATIONMENDELIAN RANDOMIZATIONPHYSICAL ACTIVITYPLASMA PROTEINSPROTEOMICSSEDENTARY BEHAVIORUK BIOBANK

Identifiers

PMID41582318
PMCPMC13117553

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.