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Molecular mechanisms linking type 2 diabetes mellitus and late-onset Alzheimer's disease: A systematic review and qualitative meta-analysis
Lemche E, Killick R, Mitchell J, Caton PW, Choudhary P, Howard JK.. Neurobiology of disease, 2024-04-21
Topic: Amyloid, tau and blood-test diagnosis
Research evidence indicating common metabolic mechanisms through which type 2 diabetes mellitus (T2DM) increases risk of late-onset Alzheimer's dementia (LOAD) has accumulated over recent decades. The aim of this systematic review is to provide a comprehensive review of common mechanisms, which have hitherto been discussed in separate perspectives, and to assemble and evaluate candidate loci and epigenetic modifications contributing to polygenic risk linkages between T2DM and LOAD. For the systematic review on pathophysiological mechanisms, both human and animal studies up to December 2023 are included. For the qualitative meta-analysis of genomic bases, human association studies were examined; for epigenetic mechanisms, data from human studies and animal models were accepted. Papers describing pathophysiological studies were identified in databases, and further literature gathered from cited work. For genomic and epigenomic studies, literature mining was conducted by formalised search codes using Boolean operators in search engines, and augmented by GeneRif citations in Entrez Gene, and other sources (WikiGenes, etc.). For the systematic review of pathophysiological mechanisms, 923 publications were evaluated, and 138 gene loci extracted for testing candidate risk linkages. 3 57 publications were evaluated for genomic association and descriptions of epigenomic modifications. Overall accumulated results highlight insulin signalling, inflammation and inflammasome pathways, proteolysis, gluconeogenesis and glycolysis, glycosylation, lipoprotein metabolism and oxidation, cell cycle regulation or survival, autophagic-lysosomal pathways, and energy. Documented findings suggest interplay between brain insulin resistance, neuroinflammation, insult compensatory mechanisms, and peripheral metabolic dysregulation in T2DM and LOAD linkage. The results allow for more streamlined longitudinal studies of T2DM-LOAD risk linkages.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Lemche, E., Killick, R., Mitchell, J., Caton, P. W., Choudhary, P., & Howard, J. K. (2024). Molecular mechanisms linking type 2 diabetes mellitus and late-onset Alzheimer's disease: A systematic review and qualitative meta-analysis. Neurobiology of disease. https://doi.org/10.1016/j.nbd.2024.106485
Vancouver
Lemche E, Killick R, Mitchell J, Caton PW, Choudhary P, Howard JK. Molecular mechanisms linking type 2 diabetes mellitus and late-onset Alzheimer's disease: A systematic review and qualitative meta-analysis. Neurobiology of disease. 2024. doi:10.1016/j.nbd.2024.106485. PMID: 38643861.
BibTeX
@article{lemche2024-38643861,
author = {Lemche, E. and Killick, R. and Mitchell, J. and Caton, P. W. and Choudhary, P. and Howard, J. K.},
title = {{Molecular mechanisms linking type 2 diabetes mellitus and late-onset Alzheimer's disease: A systematic review and qualitative meta-analysis}},
journal = {Neurobiology of disease},
year = {2024},
doi = {10.1016/j.nbd.2024.106485},
pmid = {38643861},
url = {https://doi.org/10.1016/j.nbd.2024.106485}
}
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
- Overall accumulated results highlight insulin signalling, inflammation and inflammasome pathways, proteolysis, gluconeogenesis and glycolysis, glycosylation, lipoprotein metabolism and oxidation, cell cycle regulation or survival, autophagic-lysosomal pathways, and energy.
- The results allow for more streamlined longitudinal studies of T2DM-LOAD risk linkages.
Why it matters
This review looked for shared biology between type 2 diabetes and late-onset Alzheimer's, evaluating 923 publications and pulling out 138 gene loci as possible shared risk links. The overlap centred on insulin signalling, inflammation, energy and fat metabolism, and the cell's waste-disposal (autophagy) pathways. The authors say this points to an interplay between brain insulin resistance and inflammation, and should help design more focused long-term studies.
Study details
- Study designsystematic review
- Evidence strengthHigh
How this study scored 58/100
Published in a peer-reviewed journal, and it is a systematic review of all the studies on the question. Scored zero for sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of disease) |
| Journal's citation record | 2 / 4 | Neurobiology of Disease: journal h-index 225 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A systematic review of all the studies on the question |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — 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 | A review of other studies — randomisation is not credited here |
| Times cited | 4 / 7 | Cited 41 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.2 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 3 / 6 | Cited 3.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 41 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Jane K. Howard: h-index 31 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | King's College London: institution h-index 1,348 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38643861) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 58 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.nbd.2024.106485
- PubMed: 38643861
- Original source →
- Free full text: Neurobiology of Disease →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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