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Evidence for physiological down-regulation of brain oxidative phosphorylation in Alzheimer's disease
Chandrasekaran K, Hatanpää K, Brady DR, Rapoport SI.. Experimental neurology, 1996-11-01
Topic: Amyloid, tau and blood-test diagnosis
In vivo imaging of patients with Alzheimer's disease using positron emission tomography (PET) demonstrates progressive reductions in brain glucose metabolism and blood flow in relation to dementia severity, more so in association than primary cortical regions. These reductions likely follow regional synaptic loss or dysfunction and reflect physiological down-regulation of gene expression for glucose delivery, oxidative phosphorylation (OXPHOS), and energy consumption in brain. Indeed, the pattern of down-regulation of expression for both mitochondrial and nuclear genes coding for subunits of OXPHOS enzymes in the Alzheimer brain resembles the pattern of down-regulation in normal brain caused by chronic sensory deprivation. In both cases, down-regulation likely is mediated by changes in transcriptional and posttranscriptional regulatory factors. Physiological down-regulation of OXPHOS gene expression in Alzheimer's is consistent with PET evidence that cognitive or psychophysical activation of mildly to moderately demented Alzheimer's patients can augment brain-blood flow and glucose metabolism to the same extent as in control subjects. If the primary neuronal defect that leads to reduced brain energy demand in Alzheimer's disease could be prevented or treated, brain glucose transport and OXPHOS enzyme activities might recover to normal levels.
Key findings
- These reductions likely follow regional synaptic loss or dysfunction and reflect physiological down-regulation of gene expression for glucose delivery, oxidative phosphorylation (OXPHOS), and energy consumption in brain.
- Indeed, the pattern of down-regulation of expression for both mitochondrial and nuclear genes coding for subunits of OXPHOS enzymes in the Alzheimer brain resembles the pattern of down-regulation in normal brain caused by chronic sensory deprivation.
- In both cases, down-regulation likely is mediated by changes in transcriptional and posttranscriptional regulatory factors.
- Physiological down-regulation of OXPHOS gene expression in Alzheimer's is consistent with PET evidence that cognitive or psychophysical activation of mildly to moderately demented Alzheimer's patients can augment brain-blood flow and glucose metabolism to the same extent as in control subjects.
- If the primary neuronal defect that leads to reduced brain energy demand in Alzheimer's disease could be prevented or treated, brain glucose transport and OXPHOS enzyme activities might recover to normal levels.
Study details
- Evidence strengthLow
How this study scored 36/100
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 journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Experimental neurology) |
| 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 | 1996 — 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 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 8912900) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Chandrasekaran, K., Hatanpää, K., Brady, D. R., & Rapoport, S. I. (1996). Evidence for physiological down-regulation of brain oxidative phosphorylation in Alzheimer's disease. Experimental neurology. https://doi.org/10.1006/exnr.1996.0180
Vancouver
Chandrasekaran K, Hatanpää K, Brady DR, Rapoport SI. Evidence for physiological down-regulation of brain oxidative phosphorylation in Alzheimer's disease. Experimental neurology. 1996. doi:10.1006/exnr.1996.0180. PMID: 8912900.
BibTeX
@article{chandrasekaran1996-8912900,
author = {Chandrasekaran, K. and Hatanpää, K. and Brady, D. R. and Rapoport, S. I.},
title = {{Evidence for physiological down-regulation of brain oxidative phosphorylation in Alzheimer's disease}},
journal = {Experimental neurology},
year = {1996},
doi = {10.1006/exnr.1996.0180},
pmid = {8912900},
url = {https://doi.org/10.1006/exnr.1996.0180}
}
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