Evidence map›Paper›PMID 40717458›Full record

ArticleJournal of Alzheimer's disease : JAD2025

Mid-life exposure to chronic stress accelerates cerebrovascular dysfunction and upregulates oxidative stress in Alzheimer's disease mice.

Saina S Prabhu, Emily N Burrage, Tyler Coblentz, Steven Ball, Dharendra Thapa, James W Simpkins, Evan DeVallance, Eric E Kelley, Paul D Chantler

Abstract read
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Saina S PrabhuDepartment of Pharmaceutical Sciences, West Virginia University School of Medicine, Morgantown, WV, USA.ORCID 0000-0001-9691-674X
Emily N BurrageDepartment of Neuroscience, West Virginia University School of Medicine, Morgantown, WV, USA.
Tyler CoblentzDivision of Exercise Physiology, West Virginia University School of Medicine, Morgantown, WV, USA.
Steven BallDivision of Exercise Physiology, West Virginia University School of Medicine, Morgantown, WV, USA.
Dharendra ThapaDivision of Exercise Physiology, West Virginia University School of Medicine, Morgantown, WV, USA.
James W SimpkinsDepartment of Neuroscience, West Virginia University School of Medicine, Morgantown, WV, USA.
Evan DeVallanceDepartment of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA.
Eric E KelleyDepartment of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA.
Paul D ChantlerDepartment of Neuroscience, West Virginia University School of Medicine, Morgantown, WV, USA.ORCID 0000-0001-6960-9728

Funding

West Virginia IDEA-CTRU54GM104942 · NIGMS · WEST VIRGINIA UNIVERSITY · PI Anne Courtney DeVries · 2012 to 2026
$81.0M
West Virginia University Stroke COBREP20GM109098 · NIGMS · WEST VIRGINIA UNIVERSITY · PI DEVRIES, ANNE COURTNEY · 2014 to 2024
$24.5M
Stroke and Alzheimers Disease Related DementiasT32AG052375 · NIA · WEST VIRGINIA UNIVERSITY · PI Paul D Chantler, BERNARD G. SCHREURS · 2017 to 2026
$3.5M
Psychosocial Stress-Induced Vascular Contributions To Cognitive Impairment And Alzheimer's Disease: The Role of Xanthine OxidaseR01NS117754 · NINDS · WEST VIRGINIA UNIVERSITY · PI CHANTLER, PAUL D · 2021 to 2024
$2.1M
NIA NIH HHS T32 AG052375NIGMS NIH HHS P20 GM109098NIGMS NIH HHS U54 GM104942NINDS NIH HHS R01 NS117754
6 · The paper itself

Abstract

BackgroundThis study uses the Unpredictable Chronic Mild Stress (UCMS) model to investigate the effects of mid-life stress (MLS) on vascular and neurobiological changes in triple transgenic Alzheimer's disease mice (3xTg-AD) during critical developmental stages.ObjectiveTo investigate how mid-life stress (MLS) affects cerebrovascular function and AD progression. We hypothesize that chronic stress in 3xTg-AD mice will accelerate cerebrovascular dysfunction and, subsequently, the associated AD pathology.MethodsWild-type (WT) and 3xTg-AD mice were subjected to UCMS for 8 weeks at 4 months of age, with physiological, vascular, and molecular outcomes assessed at 6 and 9 months of age. We evaluated cerebrovascular function in the middle cerebral artery (MCA) and measured the expression of key mRNA and protein alterations associated with amyloid-β (Aβ) and tau pathology, which drive AD progression.ResultsBoth WT and 3xTg-AD mice exposed to UCMS had significant MCA endothelial dysfunction. Additionally, UCMS accelerated the expression of key AD-related genes, and we observed increased oxidative stress, characterized by higher pro-oxidants and lower antioxidants. Elevated APP and BACE protein levels further suggest that MLS accelerated AD progression.ConclusionsThis study highlights the harmful effects of MLS on cerebrovascular health and the neurobiological mechanisms underlying AD progression. Our findings emphasize the critical link between chronic stress, oxidative dysfunction, and the acceleration of AD progression, offering important insights into potential therapeutic targets for alleviating the impacts of mid-life environmental stressors on AD development.

Indexed as

Alzheimer DiseaseCerebrovascular DisordersOxidative StressStress, PsychologicalAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsDisease Models, AnimalMaleMiceMice, Inbred C57BLMice, Transgenictau ProteinsUp-RegulationAmyloid beta-PeptidesAmyloid beta-Protein Precursortau ProteinsAlzheimer's diseasecerebrovascular dysfunctionmid-life chronic stressoxidative damage

Identifiers

PMID40717458
PMCPMC12892127

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Registered trials

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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.