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Tumor necrosis factor-induced cerebral insulin resistance in Alzheimer's disease links numerous treatment rationales
Clark I, Atwood C, Bowen R, Paz-Filho G, Vissel B.. Pharmacological reviews, 2012-09-10
Topic: Gut, metabolism and diet
The evident limitations of the amyloid theory of the pathogenesis of Alzheimer's disease are increasingly putting alternatives in the spotlight. We argue here that a number of independently developing approaches to therapy-including specific and nonspecific anti-tumor necrosis factor (TNF) agents, apolipoprotein E mimetics, leptin, intranasal insulin, the glucagon-like peptide-1 mimetics and glycogen synthase kinase-3 (GSK-3) antagonists-are all part of an interlocking chain of events. All these approaches inform us that inflammation and thence cerebral insulin resistance constitute the pathway on which to focus for a successful clinical outcome in treating this disease. The key link in this chain presently absent is a recognition by Alzheimer's research community of the long-neglected history of TNF induction of insulin resistance. When this is incorporated into the bigger picture, it becomes evident that the interventions we discuss are not competing alternatives but equally valid approaches to correcting different parts of the same pathway to Alzheimer's disease. These treatments can be expected to be at least additive, and conceivably synergistic, in effect. Thus the inflammation, insulin resistance, GSK-3, and mitochondrial dysfunction hypotheses are not opposing ideas but stages of the same fundamental, overarching, pathway of Alzheimer's disease pathogenesis. The insight this provides into progenitor cells, including those involved in adult neurogenesis, is a key part of this approach. This pathway also has therapeutic implications for other circumstances in which brain TNF is pathologically increased, such as stroke, traumatic brain injury, and the infectious disease encephalopathies.
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APA 7th
Clark, I., Atwood, C., Bowen, R., Paz-Filho, G., & Vissel, B. (2012). Tumor necrosis factor-induced cerebral insulin resistance in Alzheimer's disease links numerous treatment rationales. Pharmacological reviews. https://doi.org/10.1124/pr.112.005850
Vancouver
Clark I, Atwood C, Bowen R, Paz-Filho G, Vissel B. Tumor necrosis factor-induced cerebral insulin resistance in Alzheimer's disease links numerous treatment rationales. Pharmacological reviews. 2012. doi:10.1124/pr.112.005850. PMID: 22966039.
BibTeX
@article{clark2012-22966039,
author = {Clark, I. and Atwood, C. and Bowen, R. and Paz-Filho, G. and Vissel, B.},
title = {{Tumor necrosis factor-induced cerebral insulin resistance in Alzheimer's disease links numerous treatment rationales}},
journal = {Pharmacological reviews},
year = {2012},
doi = {10.1124/pr.112.005850},
pmid = {22966039},
url = {https://doi.org/10.1124/pr.112.005850}
}
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Key findings
- When this is incorporated into the bigger picture, it becomes evident that the interventions we discuss are not competing alternatives but equally valid approaches to correcting different parts of the same pathway to Alzheimer's disease.
- These treatments can be expected to be at least additive, and conceivably synergistic, in effect.
- Thus the inflammation, insulin resistance, GSK-3, and mitochondrial dysfunction hypotheses are not opposing ideas but stages of the same fundamental, overarching, pathway of Alzheimer's disease pathogenesis.
- The insight this provides into progenitor cells, including those involved in adult neurogenesis, is a key part of this approach.
- This pathway also has therapeutic implications for other circumstances in which brain TNF is pathologically increased, such as stroke, traumatic brain injury, and the infectious disease encephalopathies.
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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 (Pharmacological reviews) |
| 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 | 2012 — 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) |
| 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 22966039) |
| 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 | — |
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