Home › Research › Disease mechanisms
Oxidative Stress Hypothesis in Alzheimer's Disease
William R. Markesbery. Free Radical Biology and Medicine, 1997
Topic: Amyloid, tau and blood-test diagnosis
This study examined evidence regarding the oxidative stress hypothesis in Alzheimer's disease. It reviewed direct and indirect evidence indicating that the brain in Alzheimer's disease is under increased oxidative stress. The findings indicate that free radicals are possibly involved in the pathogenesis of neuron degeneration and death in Alzheimer's disease.
Key findings
- The direct evidence supporting increased oxidative stress in AD is: (1) increased brain Fe, Al, and Hg in AD, capable of stimulating free radical generation; (2) increased lipid peroxidation and decreased polyunsaturated fatty acids in the AD brain, and increased 4-hydroxynonenal, an aldehyde product of lipid peroxidation in AD ventricular fluid; (3) increased protein and DNA oxidation in the AD brain; (4) diminished energy metabolism and decreased cytochrome c oxidase in the brain in AD; (5) advanced glycation end products (AGE), malondialdehyde, carbonyls, peroxynitrite, heme oxygenase-1 and SOD-1 in neurofibrillary tangles and AGE, heme oxygenase-1, SOD-1 in senile plaques; and (6) studies showing that amyloid beta peptide is capable of generating free radicals.
- Supporting indirect evidence comes from a variety of in vitro studies showing that free radicals are capable of mediating neuron degeneration and death.
- Overall, these studies indicate that free radicals are possibly involved in the pathogenesis of neuron death in AD.
- Even if free radical generation is secondary to other initiating causes, they are deleterious and part of a cascade of events that can lead to neuron death, suggesting that therapeutic efforts aimed at removal of ROS or prevention of their formation may be beneficial in AD.
Why it matters
Discusses the oxidative stress hypothesis in Alzheimer's disease.
How this study scored 52/100
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 strength of evidence and institution's track record, so those were left out: it earned 48 of the 92 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Free Radical Biology and 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 | — / 5 | No evidence rating recorded — left out of this score |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 1997 — 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 | 7 / 7 | Cited 2,385 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 76.9 citations a year over 31 year(s) since 1997 |
| Impact for its field and year | 6 / 6 | Cited 42.4× 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 | 3 / 4 | Cited 120 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author William R. Markesbery: h-index 124 (OpenAlex, whole career) |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 0 institution(s) in 0 countries — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 9165306) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 48 / 92 | Scored on 18 of 20 parts. We have no data for the rest, so they are left out: 48 of the 92 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.
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. Check the citation against the original before you use it.
APA 7th
Markesbery, W. R. (1997). Oxidative Stress Hypothesis in Alzheimer's Disease. Free Radical Biology and Medicine. https://doi.org/10.1016/s0891-5849(96)00629-6
Vancouver
Markesbery WR. Oxidative Stress Hypothesis in Alzheimer's Disease. Free Radical Biology and Medicine. 1997. doi:10.1016/s0891-5849(96)00629-6. PMID: 9165306.
BibTeX
@article{markesbery1997-9165306,
author = {Markesbery, William R.},
title = {{Oxidative Stress Hypothesis in Alzheimer's Disease}},
journal = {Free Radical Biology and Medicine},
year = {1997},
doi = {10.1016/s0891-5849(96)00629-6},
pmid = {9165306},
url = {https://doi.org/10.1016/s0891-5849(96)00629-6}
}
Related studies in Disease mechanisms
Also in Disease mechanisms
128 studies in the library are filed under Disease mechanisms with no topic tag they share with another; these are this study's neighbours in a fixed tour of them. The Disease mechanisms hub.