Oxidative damage and protection by antioxidants in the frontal cortex of Alzheimer's disease is related to the apolipoprotein E genotype
Ramassamy C, Averill D, Beffert U, Bastianetto S, Theroux L, Lussier-Cacan S, Cohn JS, Christen Y et al.. Free radical biology & medicine, 1999-09-01
Topic: Amyloid, tau and blood-test diagnosis
A great number of epidemiological studies have demonstrated that the frequency of the epsilon4 allele of the apolipoprotein E gene (APOE) is markedly higher in sporadic and in familial late onset Alzheimer disease (AD). In the frontal cortex of AD patients, oxidative damage is elevated. We address the hypothesis that the APOE genotype and reactive oxygen-mediated damage are linked in the frontal cortex of AD patients. We have related the APOE genotype to the levels of lipid oxidation (LPO) and to the antioxidant status, in frontal cortex tissues from age-matched control and AD cases with different APOE genotypes. LPO levels were significantly elevated in tissues from Alzheimer's cases which are homozygous for the epsilon4 allele of APOE, compared to AD epsilon3/epsilon3 cases and controls. Activities of enzymatic antioxidants, such as catalase and glutathione peroxidase (GSH-PX), were also higher in AD cases with at least one epsilon4 allele of APOE, while superoxide dismutase (SOD) activity was unchanged. In the frontal cortex, the concentration of apoE protein was not different between controls and AD cases, and was genotype independent. The Ginkgo biloba extract (EGb 761), the neurosteroid dehydroepiandrosterone (DHEA) and human recombinant apoE3 (hapoE3rec) were able to protect control, AD epsilon3/epsilon3 and epsilon3/epsilon4 cases against hydrogen peroxide/iron-induced LPO, while hapoE4rec was completely ineffective. Moreover, EGb 761 and DHEA had no effect in homozygous epsilon4 cases. These results demonstrate that oxidative stress-induced injury and protection by antioxidants in the frontal cortex of AD cases are related to the APOE genotype.
Key findings
- A great number of epidemiological studies have demonstrated that the frequency of the epsilon4 allele of the apolipoprotein E gene (APOE) is markedly higher in sporadic and in familial late onset Alzheimer disease (AD).
- LPO levels were significantly elevated in tissues from Alzheimer's cases which are homozygous for the epsilon4 allele of APOE, compared to AD epsilon3/epsilon3 cases and controls.
- These results demonstrate that oxidative stress-induced injury and protection by antioxidants in the frontal cortex of AD cases are related to the APOE genotype.
Why it matters
In frontal cortex tissue from Alzheimer's disease patients, lipid oxidation was significantly elevated in those homozygous for the APOE ε4 allele compared with APOE ε3/ε3 cases and controls, and the antioxidants EGb 761, DHEA, and human recombinant apoE3 protected tissue against hydrogen peroxide/iron-induced damage. This is tissue-level research and does not show that any antioxidant prevents or treats Alzheimer's disease in people.
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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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Free radical biology & medicine) |
| Journal's citation record | 3 / 4 | Free Radical Biology and Medicine: journal h-index 378 (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 | 1999 — 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 | 5 / 7 | Cited 242 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.3 citations a year over 29 year(s) since 1999 |
| Impact for its field and year | 4 / 6 | Cited 9.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Judes Poirier: h-index 62 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | McGill University: institution h-index 1,373 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10490274) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 45 / 100 | — |
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APA 7th
Ramassamy, C., Averill, D., Beffert, U., Bastianetto, S., Theroux, L., Lussier-Cacan, S., et al. (1999). Oxidative damage and protection by antioxidants in the frontal cortex of Alzheimer's disease is related to the apolipoprotein E genotype. Free radical biology & medicine. https://doi.org/10.1016/s0891-5849(99)00102-1
Vancouver
Ramassamy C, Averill D, Beffert U, Bastianetto S, Theroux L, Lussier-Cacan S, et al. Oxidative damage and protection by antioxidants in the frontal cortex of Alzheimer's disease is related to the apolipoprotein E genotype. Free radical biology & medicine. 1999. doi:10.1016/s0891-5849(99)00102-1. PMID: 10490274.
BibTeX
@article{ramassamy1999-10490274,
author = {Ramassamy, C. and Averill, D. and Beffert, U. and Bastianetto, S. and Theroux, L. and Lussier-Cacan, S. and Cohn, J. S. and Christen, Y. and others},
title = {{Oxidative damage and protection by antioxidants in the frontal cortex of Alzheimer's disease is related to the apolipoprotein E genotype}},
journal = {Free radical biology \& medicine},
year = {1999},
doi = {10.1016/s0891-5849(99)00102-1},
pmid = {10490274},
url = {https://doi.org/10.1016/s0891-5849(99)00102-1}
}
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