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Hyperhomocysteinemia increases beta-amyloid by enhancing expression of gamma-secretase and phosphorylation of amyloid precursor protein in rat brain
Zhang CE, Wei W, Liu YH, Peng JH, Tian Q, Liu GP, Zhang Y, Wang JZ.. The American journal of pathology, 2009-03-05
Topic: Brain proteins, microglia and lab models
Hyperhomocysteinemia and beta-amyloid (Abeta) overproduction are critical etiological and pathological factors in Alzheimer disease, respectively; however, the intrinsic link between them is still missing. Here, we found that Abeta levels increased and amyloid precursor protein (APP) levels simultaneously decreased in hyperhomocysteinemic rats after a 2-week induction by vena caudalis injection of homocysteine. Concurrently, both the mRNA and protein levels of presenilin-1, a component of gamma-secretase, were elevated, whereas the expression levels of beta-secretase and presenilin-2 were not altered.
Key findings
- Here, we found that Abeta levels increased and amyloid precursor protein (APP) levels simultaneously decreased in hyperhomocysteinemic rats after a 2-week induction by vena caudalis injection of homocysteine.
- Concurrently, both the mRNA and protein levels of presenilin-1, a component of gamma-secretase, were elevated, whereas the expression levels of beta-secretase and presenilin-2 were not altered.
- We also observed that levels of phosphorylated APP at threonine-668, a crucial site facilitating the amyloidogenic cleavage of APP, increased in rats with hyperhomocysteinemia, although the phosphorylation per se did not increase the binding capacity of pT668-APP to the secretases.
- The enhanced phosphorylation of APP in these rats was not relevant to either c-Jun N-terminal kinase or cyclin-dependent kinase-5.
Why it matters
In rats, high homocysteine raised amyloid-beta levels and increased presenilin-1, part of gamma-secretase. This is an animal finding about a possible mechanism and does not show that lowering homocysteine treats or prevents Alzheimer's disease in people.
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Study details
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The American journal of pathology) |
| Journal's citation record | 3 / 4 | American Journal Of Pathology: journal h-index 328 (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 | 1 / 5 | 2009 — within 20 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 | Laboratory or animal study (title names “rat”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 151 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.9 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 3 / 6 | Cited 7.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 19 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Jian‐Zhi Wang: h-index 58 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Huazhong University of Science and Technology: institution h-index 934 (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 19264913) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 40 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Zhang, C. E., Wei, W., Liu, Y. H., Peng, J. H., Tian, Q., Liu, G. P., et al. (2009). Hyperhomocysteinemia increases beta-amyloid by enhancing expression of gamma-secretase and phosphorylation of amyloid precursor protein in rat brain. The American journal of pathology. https://doi.org/10.2353/ajpath.2009.081036
Vancouver
Zhang CE, Wei W, Liu YH, Peng JH, Tian Q, Liu GP, et al. Hyperhomocysteinemia increases beta-amyloid by enhancing expression of gamma-secretase and phosphorylation of amyloid precursor protein in rat brain. The American journal of pathology. 2009. doi:10.2353/ajpath.2009.081036. PMID: 19264913.
BibTeX
@article{zhang2009-19264913,
author = {Zhang, C. E. and Wei, W. and Liu, Y. H. and Peng, J. H. and Tian, Q. and Liu, G. P. and Zhang, Y. and Wang, J. Z.},
title = {{Hyperhomocysteinemia increases beta-amyloid by enhancing expression of gamma-secretase and phosphorylation of amyloid precursor protein in rat brain}},
journal = {The American journal of pathology},
year = {2009},
doi = {10.2353/ajpath.2009.081036},
pmid = {19264913},
url = {https://doi.org/10.2353/ajpath.2009.081036}
}
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