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Oxidative Stress as a Central Mechanistic Bridge Between Alzheimer’s and Vascular Pathologies in Mixed Dementia: Emerging Evidence and Therapeutic Perspectives
Francesca Beretti, Marta Malenchini, Martina Gatti, Tullia Maraldi. Biomedicines, 2025-12-26
Topic: Amyloid, tau and blood-test diagnosis
Mixed dementia (MD), characterized by overlapping features of Alzheimer's disease (AD) and vascular dementia (VaD), represents the most prevalent form of late-life cognitive decline. Increasing evidence identifies oxidative stress as a unifying molecular mechanism driving both neurodegenerative and vascular pathologies in MD. Reactive oxygen species (ROS) contribute to amyloid-β aggregation, tau hyperphosphorylation, endothelial dysfunction, and blood-brain barrier disruption, creating a self-perpetuating cycle of neuronal and vascular injury. Mechanistic models demonstrate how chronic hypoperfusion and mitochondrial dysfunction exacerbate ROS generation and neuroinflammation, while impaired Nrf2-mediated antioxidant defense further amplifies damage. Therapeutically, classical antioxidants show inconsistent efficacy, shifting focus toward mitochondrial protection, Nrf2 activation, and lifestyle-based oxidative load reduction. Therefore, we sought to outline therapeutic approaches capable of broadly targeting these mechanisms, through focused narrative analysis of recent studies employing delivery systems for antioxidant proteins and/or redox-regulating miRNAs. In particular, experimental interventions using mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) demonstrate neuroprotective and anti-inflammatory effects via the Nrf2 pathway, suggesting promising avenues for multimodal treatment. Integrating oxidative, vascular, and neurodegenerative paradigms is essential for advancing diagnostic precision and developing targeted interventions capable of addressing the complex pathophysiology of mixed dementia.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Beretti, F., Malenchini, M., Gatti, M., & Maraldi, T. (2025). Oxidative Stress as a Central Mechanistic Bridge Between Alzheimer’s and Vascular Pathologies in Mixed Dementia: Emerging Evidence and Therapeutic Perspectives. Biomedicines. https://doi.org/10.3390/biomedicines14010059
Vancouver
Beretti F, Malenchini M, Gatti M, Maraldi T. Oxidative Stress as a Central Mechanistic Bridge Between Alzheimer’s and Vascular Pathologies in Mixed Dementia: Emerging Evidence and Therapeutic Perspectives. Biomedicines. 2025. doi:10.3390/biomedicines14010059. PMID: 41595595.
BibTeX
@article{beretti2025-41595595,
author = {Beretti, Francesca and Malenchini, Marta and Gatti, Martina and Maraldi, Tullia},
title = {{Oxidative Stress as a Central Mechanistic Bridge Between Alzheimer’s and Vascular Pathologies in Mixed Dementia: Emerging Evidence and Therapeutic Perspectives}},
journal = {Biomedicines},
year = {2025},
doi = {10.3390/biomedicines14010059},
pmid = {41595595},
url = {https://doi.org/10.3390/biomedicines14010059}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Mechanistic models demonstrate how chronic hypoperfusion and mitochondrial dysfunction exacerbate ROS generation and neuroinflammation, while impaired Nrf2-mediated antioxidant defense further amplifies damage.
- Therapeutically, classical antioxidants show inconsistent efficacy, shifting focus toward mitochondrial protection, Nrf2 activation, and lifestyle-based oxidative load reduction.
- Therefore, we sought to outline therapeutic approaches capable of broadly targeting these mechanisms, through focused narrative analysis of recent studies employing delivery systems for antioxidant proteins and/or redox-regulating miRNAs.
- In particular, experimental interventions using mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) demonstrate neuroprotective and anti-inflammatory effects via the Nrf2 pathway, suggesting promising avenues for multimodal treatment.
- Integrating oxidative, vascular, and neurodegenerative paradigms is essential for advancing diagnostic precision and developing targeted interventions capable of addressing the complex pathophysiology of mixed dementia.
Why it matters
This review proposes oxidative stress as a shared mechanism in mixed dementia and discusses experimental approaches such as mitochondrial protection, Nrf2 activation, and stem cell-derived extracellular vesicles. It is a narrative review, so it does not show that any of these approaches treat or prevent Alzheimer's disease in patients.
Study details
- Evidence strengthLow
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biomedicines) |
| Journal's citation record | 1 / 4 | Biomedicines: journal h-index 133 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 9 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Tullia Maraldi: h-index 31 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Bologna: institution h-index 989 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41595595) |
| Free to read | 2 / 2 | Free to read |
| Total | 39 / 100 | — |
What each of these 20 components measures, and what this score is not →
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