Home › Research › Mild cognitive impairment
Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer's disease
Mota SI, Costa RO, Ferreira IL, Santana I, Caldeira GL, Padovano C, Fonseca AC, Baldeiras I et al.. Biochimica et biophysica acta, 2015-04-06
Topic: Amyloid, tau and blood-test diagnosis
Oxidative stress and endoplasmic reticulum (ER) stress have been associated with Alzheimer's disease (AD) progression. In this study we analyzed whether oxidative stress involving changes in Nrf2 and ER stress may constitute early events in AD pathogenesis by using human peripheral blood cells and an AD transgenic mouse model at different disease stages. Increased oxidative stress and increased phosphorylated Nrf2 (p(Ser40)Nrf2) were observed in human peripheral blood mononuclear cells (PBMCs) isolated from individuals with mild cognitive impairment (MCI). Moreover, we observed impaired ER Ca2+ homeostasis and increased ER stress markers in PBMCs from MCI individuals and mild AD patients. Evidence of early oxidative stress defense mechanisms in AD was substantiated by increased p(Ser40)Nrf2 in 3month-old 3xTg-AD male mice PBMCs, and also with increased nuclear Nrf2 levels in brain cortex. However, SOD1 protein levels were decreased in human MCI PBMCs and in 3xTg-AD mice brain cortex; the latter further correlated with reduced SOD1 mRNA levels. Increased ER stress was also detected in the brain cortex of young female and old male 3xTg-AD mice. We demonstrate oxidative stress and early Nrf2 activation in AD human and mouse models, which fails to regulate some of its targets, leading to repressed expression of antioxidant defenses (e.g., SOD-1), and extending to ER stress. Results suggest markers of prodromal AD linked to oxidative stress associated with Nrf2 activation and ER stress that may be followed in human peripheral blood mononuclear cells.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Mota, S. I., Costa, R. O., Ferreira, I. L., Santana, I., Caldeira, G. L., Padovano, C., et al. (2015). Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer's disease. Biochimica et biophysica acta. https://doi.org/10.1016/j.bbadis.2015.03.015
Vancouver
Mota SI, Costa RO, Ferreira IL, Santana I, Caldeira GL, Padovano C, et al. Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer's disease. Biochimica et biophysica acta. 2015. doi:10.1016/j.bbadis.2015.03.015. PMID: 25857617.
BibTeX
@article{mota2015-25857617,
author = {Mota, S. I. and Costa, R. O. and Ferreira, I. L. and Santana, I. and Caldeira, G. L. and Padovano, C. and Fonseca, A. C. and Baldeiras, I. and others},
title = {{Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer's disease}},
journal = {Biochimica et biophysica acta},
year = {2015},
doi = {10.1016/j.bbadis.2015.03.015},
pmid = {25857617},
url = {https://doi.org/10.1016/j.bbadis.2015.03.015}
}
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Oxidative stress and endoplasmic reticulum (ER) stress have been associated with Alzheimer's disease (AD) progression.
- Moreover, we observed impaired ER Ca2+ homeostasis and increased ER stress markers in PBMCs from MCI individuals and mild AD patients.
- Results suggest markers of prodromal AD linked to oxidative stress associated with Nrf2 activation and ER stress that may be followed in human peripheral blood mononuclear cells.
Why it matters
In blood immune cells from people with mild cognitive impairment, this lab study found more oxidative stress and an activated form of the cell's antioxidant switch, Nrf2, yet lower levels of the antioxidant enzyme SOD1. It also found signs of stress in the cell's protein-folding machinery (ER stress), both in MCI and in mild Alzheimer's, with related changes in an Alzheimer's mouse model. The authors suggest these may be early markers that "may be followed" in blood, but the study did not test a diagnostic or any treatment.
Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, so that was left out: it earned 41 of the 96 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biochimica et biophysica acta) |
| 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 | 2015 — 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 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 185 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.2 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 13.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 2 / 4 | Cited 32 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Ana Cristina Rego: h-index 56 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | University of Coimbra: institution h-index 515 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25857617) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 41 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 41 of the 96 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.bbadis.2015.03.015
- PubMed: 25857617
- Original source →
- Free full text: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Related
Studies in the library that share something with this one. The line above each title says what.
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
7 studies in the alzhub library list this one in their references.
Related studies in Mild cognitive impairment
Also tagged “precursor”
1,337 studies in the library carry the topic tag “precursor”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,337 tagged studies.