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From metabolic dysregulation to neurodegenerative pathology: the role of hyperglycemia, oxidative stress, and blood-brain barrier breakdown in T2D-driven Alzheimer's disease
Raza A, Saleem S, Imran S, Rahman S, Haroon M, Razzaq A, Hussain A, Iqbal J et al.. Metabolic brain disease, 2025-09-26
Topic: Brain proteins, microglia and lab models
Type 2 Diabetes (T2D) and Alzheimer's Disease (AD) share common risk factors that can be seen through T2D nearly doubling an individual's likelihood of developing AD. Some AD patients show signs of metabolic dysfunction as well. This review focuses on the potential mechanisms associated with these two diseases, like insulin resistance, inflammation, oxidative damage, mitochondrial injury, and cell death. One of the notable elements in this connection is the "brain insulin resistance," most frequently named as "type 3 diabetes," which impairs glucose metabolism and facilitates amyloid beta (Aβ) plaque synthesis while reducing the action of insulin-degrading enzyme (IDE). Moreover, the overactivity of glycogen synthase kinase-3 beta (GSK-3β) also triggers taurine protein pathology. Raised concentrations of glucose in blood can produce advanced glycation end products (AGEs), which further exacerbate neuroinflammation in tandem with the mitigation of neurotoxic Aβ oligomers. Inflammation and subsequent damage to mitochondria lead to the dissolution of synapses. Current vascular insults include the breakdown of the blood-brain barrier (BBB) and decreased brain perfusion, along with other contributory factors to conditions conducive to neurotoxicity. Recently, novel therapies are emerging, including GLP-1 agonists, intranasal insulin, and mitochondrial antioxidants, that show surprising results for treating both conditions, but on the contrary, bioavailability and the timing of interventions remain a big challenge in the management of these diseases. Eventually, further research should center on understanding the mechanisms of integration along with the development of molecular biology, neuroimaging, and outcome-driven treatment strategies. Comprehensive strategies that exist between T2D-AD for integration and preservation of brain and metabolic health are addressed in this review.
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APA 7th
Raza, A., Saleem, S., Imran, S., Rahman, S., Haroon, M., Razzaq, A., et al. (2025). From metabolic dysregulation to neurodegenerative pathology: the role of hyperglycemia, oxidative stress, and blood-brain barrier breakdown in T2D-driven Alzheimer's disease. Metabolic brain disease. https://doi.org/10.1007/s11011-025-01700-z
Vancouver
Raza A, Saleem S, Imran S, Rahman S, Haroon M, Razzaq A, et al. From metabolic dysregulation to neurodegenerative pathology: the role of hyperglycemia, oxidative stress, and blood-brain barrier breakdown in T2D-driven Alzheimer's disease. Metabolic brain disease. 2025. doi:10.1007/s11011-025-01700-z. PMID: 41003796.
BibTeX
@article{raza2025-41003796,
author = {Raza, A. and Saleem, S. and Imran, S. and Rahman, S. and Haroon, M. and Razzaq, A. and Hussain, A. and Iqbal, J. and others},
title = {{From metabolic dysregulation to neurodegenerative pathology: the role of hyperglycemia, oxidative stress, and blood-brain barrier breakdown in T2D-driven Alzheimer's disease}},
journal = {Metabolic brain disease},
year = {2025},
doi = {10.1007/s11011-025-01700-z},
pmid = {41003796},
url = {https://doi.org/10.1007/s11011-025-01700-z}
}
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Key findings
- This review focuses on the potential mechanisms associated with these two diseases, like insulin resistance, inflammation, oxidative damage, mitochondrial injury, and cell death.
- Recently, novel therapies are emerging, including GLP-1 agonists, intranasal insulin, and mitochondrial antioxidants, that show surprising results for treating both conditions, but on the contrary, bioavailability and the timing of interventions remain a big challenge in the management of these diseases.
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Study details
- Evidence strengthLow
How this study scored 45/100
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. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 26 of the 58 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Metabolic brain disease) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41003796) |
| Free to read | 2 / 2 | Free to read |
| Points | 26 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 58 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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