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Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease
Butterfield DA, Halliwell B.. Nature reviews. Neuroscience, 2019-03-01
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer disease (AD) is a major cause of age-related dementia. We do not fully understand AD aetiology and pathogenesis, but oxidative damage is a key component. The brain mostly uses glucose for energy, but in AD and amnestic mild cognitive impairment glucose metabolism is dramatically decreased, probably owing, at least in part, to oxidative damage to enzymes involved in glycolysis, the tricarboxylic acid cycle and ATP biosynthesis. Consequently, ATP-requiring processes for cognitive function are impaired, and synaptic dysfunction and neuronal death result, with ensuing thinning of key brain areas. We summarize current research on the interplay and sequence of these processes and suggest potential pharmacological interventions to retard AD progression.
Key findings
- Consequently, ATP-requiring processes for cognitive function are impaired, and synaptic dysfunction and neuronal death result, with ensuing thinning of key brain areas.
Why it matters
This review pulls together research suggesting that in Alzheimer's disease and amnestic mild cognitive impairment, the brain's use of glucose is "dramatically decreased", which the authors say is "probably owing, at least in part" to oxidative damage to the enzymes that make energy (ATP). They describe a proposed chain in which less energy weakens synapses and kills neurons, leading to thinning of key brain areas. It is a summary of existing work, not a new study: it reports no patient data and no tested treatment, and the drug ideas it raises are only "potential" ways to slow the disease.
Study details
- Evidence strengthLow
How this study scored 57/100
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 (Nature reviews. Neuroscience) |
| Journal's citation record | 4 / 4 | Nature reviews. Neuroscience: journal h-index 572 (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 | 2 / 5 | 2019 — within 10 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 | 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 1,948 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 216.4 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 5 / 6 | Cited 29.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 30 other studies in this library |
| Still being cited | 4 / 4 | Cited 948 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Barry B. Halliwell: h-index 192 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | National University of Singapore: institution h-index 1,166 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30737462) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Butterfield, D. A., & Halliwell, B. (2019). Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease. Nature reviews. Neuroscience. https://doi.org/10.1038/s41583-019-0132-6
Vancouver
Butterfield DA, Halliwell B. Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease. Nature reviews. Neuroscience. 2019. doi:10.1038/s41583-019-0132-6. PMID: 30737462.
BibTeX
@article{butterfield2019-30737462,
author = {Butterfield, D. A. and Halliwell, B.},
title = {{Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease}},
journal = {Nature reviews. Neuroscience},
year = {2019},
doi = {10.1038/s41583-019-0132-6},
pmid = {30737462},
url = {https://doi.org/10.1038/s41583-019-0132-6}
}
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