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S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production
Fuso A, Seminara L, Cavallaro RA, D'Anselmi F, Scarpa S.. Molecular and cellular neurosciences, 2005-01-01
Topic: Brain proteins, microglia and lab models
Few diseases are characterized by high homocysteine (HCY) and low folate and vitamin B12 blood levels. It has already been shown that DNA methylation is involved in amyloid precursor protein (APP) processing and beta-amyloid (A beta) production through the regulation of Presenilin1 (PS1) expression and that exogenous S-adenosylmethionine (SAM) can silence the gene reducing A beta production. Here we demonstrate that BACE (beta-secretase), as well as PS1, is regulated by methylation and that the reduction of folate and vitamin B12 in culture medium can cause a reduction of SAM levels with consequent increase in presenilin1 and BACE levels and with increase in A beta production.
Key findings
- It has already been shown that DNA methylation is involved in amyloid precursor protein (APP) processing and beta-amyloid (A beta) production through the regulation of Presenilin1 (PS1) expression and that exogenous S-adenosylmethionine (SAM) can silence the gene reducing A beta production.
- Here we demonstrate that BACE (beta-secretase), as well as PS1, is regulated by methylation and that the reduction of folate and vitamin B12 in culture medium can cause a reduction of SAM levels with consequent increase in presenilin1 and BACE levels and with increase in A beta production.
- The simultaneous administration of SAM to the deficient medium can restore the normal gene expression, thus reducing the A beta levels.
- The use of deprived medium was intended to mimic a mild nutritional deficit involved in the onset of AD.
Why it matters
In cultured cells, lowering folate and vitamin B12 reduced SAM levels, which increased presenilin 1 and BACE levels and raised amyloid beta production. This is cell-culture work linking the homocysteine cycle and DNA methylation to amyloid production, not proof that vitamin supplements prevent Alzheimer's.
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Study details
- Evidence strengthLow
How this study scored 44/100
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, so that was left out: it earned 42 of the 96 points we could judge it on, which is 44 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular and cellular neurosciences) |
| 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 | 1 / 5 | 2005 — older than 20 years, still counted |
| 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 | 6 / 7 | Cited 407 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 17.7 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 4 / 6 | Cited 8.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 2 / 4 | Cited 29 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Sigfrido Scarpa: h-index 29 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Sapienza University of Rome: institution h-index 1,145 (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 15607954) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 42 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 42 of the 96 points we could judge it on is 44 out of 100. |
| Total | 44 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Fuso, A., Seminara, L., Cavallaro, R. A., D'Anselmi, F., & Scarpa, S. (2005). S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production. Molecular and cellular neurosciences. https://doi.org/10.1016/j.mcn.2004.09.007
Vancouver
Fuso A, Seminara L, Cavallaro RA, D'Anselmi F, Scarpa S. S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production. Molecular and cellular neurosciences. 2005. doi:10.1016/j.mcn.2004.09.007. PMID: 15607954.
BibTeX
@article{fuso2005-15607954,
author = {Fuso, A. and Seminara, L. and Cavallaro, R. A. and D'Anselmi, F. and Scarpa, S.},
title = {{S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production}},
journal = {Molecular and cellular neurosciences},
year = {2005},
doi = {10.1016/j.mcn.2004.09.007},
pmid = {15607954},
url = {https://doi.org/10.1016/j.mcn.2004.09.007}
}
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