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Sex differences in the progression of glucose metabolism dysfunction in Alzheimer's disease
Park JC, Lim H, Byun MS, Yi D, Byeon G, Jung G, Kim YK, Lee DY et al.. Experimental & molecular medicine, 2023-05-01
Topic: Genetics and APOE
Alzheimer's disease (AD) is a common neurodegenerative disease characterized by amyloid plaques and impaired brain metabolism. Because women have a higher prevalence of AD than men, sex differences are of great interest. Using cross-sectional and longitudinal data, we showed sex-dependent metabolic dysregulations in the brains of AD patients. Cohort 1 (South Korean, n = 181) underwent Pittsburgh compound B-PET, fluorodeoxyglucose-PET, magnetic resonance imaging, and blood biomarker (plasma tau and beta-amyloid 42 and 40) measurements at baseline and two-year follow-ups. Transcriptome analysis of data from Cohorts 2 and 3 (European, n = 78; Singaporean, n = 18) revealed sex differences in AD-related alterations in brain metabolism. In women (but not in men), all imaging indicators displayed consistent correlation curves with AD progression. At the two-year follow-up, clear brain metabolic impairment was revealed only in women, and the plasma beta-amyloid 42/40 ratio was a possible biomarker for brain metabolism in women. Furthermore, our transcriptome analysis revealed sex differences in transcriptomes and metabolism in the brains of AD patients as well as a molecular network of 25 female-specific glucose metabolic genes (FGGs). We discovered four key-attractor FGG genes (ALDOA, ENO2, PRKACB, and PPP2R5D) that were associated with amyloid/tau-related genes (APP, MAPT, BACE1, and BACE2). Furthermore, these genes successfully distinguished amyloid positivity in women. Understanding sex differences in the pathogenesis of AD and considering these differences will improve development of effective diagnostics and therapeutic treatments for AD.
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APA 7th
Park, J. C., Lim, H., Byun, M. S., Yi, D., Byeon, G., Jung, G., et al. (2023). Sex differences in the progression of glucose metabolism dysfunction in Alzheimer's disease. Experimental & molecular medicine. https://doi.org/10.1038/s12276-023-00993-3
Vancouver
Park JC, Lim H, Byun MS, Yi D, Byeon G, Jung G, et al. Sex differences in the progression of glucose metabolism dysfunction in Alzheimer's disease. Experimental & molecular medicine. 2023. doi:10.1038/s12276-023-00993-3. PMID: 37121979.
BibTeX
@article{park2023-37121979,
author = {Park, J. C. and Lim, H. and Byun, M. S. and Yi, D. and Byeon, G. and Jung, G. and Kim, Y. K. and Lee, D. Y. and others},
title = {{Sex differences in the progression of glucose metabolism dysfunction in Alzheimer's disease}},
journal = {Experimental \& molecular medicine},
year = {2023},
doi = {10.1038/s12276-023-00993-3},
pmid = {37121979},
url = {https://doi.org/10.1038/s12276-023-00993-3}
}
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Key findings
- Transcriptome analysis of data from Cohorts 2 and 3 (European, n = 78; Singaporean, n = 18) revealed sex differences in AD-related alterations in brain metabolism.
- At the two-year follow-up, clear brain metabolic impairment was revealed only in women, and the plasma beta-amyloid 42/40 ratio was a possible biomarker for brain metabolism in women.
- Furthermore, our transcriptome analysis revealed sex differences in transcriptomes and metabolism in the brains of AD patients as well as a molecular network of 25 female-specific glucose metabolic genes (FGGs).
- We discovered four key-attractor FGG genes (ALDOA, ENO2, PRKACB, and PPP2R5D) that were associated with amyloid/tau-related genes (APP, MAPT, BACE1, and BACE2).
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Study details
- Study designcross-sectional
- Participants181
- Evidence strengthModerate
How this study scored 62/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for effect reported 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 36 of the 58 points we could judge it on, which is 62 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Experimental & molecular medicine) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 181 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| 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 37121979) |
| Free to read | 2 / 2 | Free to read |
| Points | 36 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 36 of the 58 points we could judge it on is 62 out of 100. |
| Total | 62 / 100 | — |
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