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Reimagining Alzheimer's disease--an age-based hypothesis
Herrup K.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010-12-01
Topic: Disease mechanisms in lab and animal studies
The historical roots of Alzheimer's disease provide a sound conceptual basis for linking the behavioral and neurological symptoms of the disease with the frequently associated pathology of amyloid plaques and neurofibrillary tangles. Out of these roots has grown the "amyloid cascade hypothesis"--a vision of the etiology of Alzheimer's that has spurred the discovery of many important insights into the neurobiology of the disease. Despite these successes, the wealth of new data now available to biomedical researchers urges a full review of the origins of Alzheimer's, and such a reconsideration is offered here. It begins with the most widely accepted risk factor for developing Alzheimer's disease: age. Then, for an individual to progress from normal age-appropriate cognitive function to a condition where the full palette of clinical symptoms is expressed, three key steps are envisioned: (1) an initiating injury, (2) a chronic neuroinflammatory response, and (3) a discontinuous cellular change of state involving most, if not all, of the cell types of the brain. The amyloid cascade is integrated into this sequence, but reconfigured as an amyloid deposition cycle. In this way, the pathology of amyloid plaques is envisioned as highly correlated with, but mechanistically distinct from, the three obligatory steps leading to Alzheimer's disease. The implications of this new model are discussed with respect to our current diagnostic criteria, and suggestions are put forward for expanding our future research efforts.
Key findings
- It begins with the most widely accepted risk factor for developing Alzheimer's disease: age.
- Then, for an individual to progress from normal age-appropriate cognitive function to a condition where the full palette of clinical symptoms is expressed, three key steps are envisioned: (1) an initiating injury, (2) a chronic neuroinflammatory response, and (3) a discontinuous cellular change of state involving most, if not all, of the cell types of the brain.
- The amyloid cascade is integrated into this sequence, but reconfigured as an amyloid deposition cycle.
- In this way, the pathology of amyloid plaques is envisioned as highly correlated with, but mechanistically distinct from, the three obligatory steps leading to Alzheimer's disease.
- The implications of this new model are discussed with respect to our current diagnostic criteria, and suggestions are put forward for expanding our future research efforts.
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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 (The Journal of neuroscience : the official journal of the Society for Neuroscience) |
| 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 | 2010 — 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 21159946) |
| 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
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
Herrup, K. (2010). Reimagining Alzheimer's disease--an age-based hypothesis. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.4521-10.2010
Vancouver
Herrup K. Reimagining Alzheimer's disease--an age-based hypothesis. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2010. doi:10.1523/jneurosci.4521-10.2010. PMID: 21159946.
BibTeX
@article{herrup2010-21159946,
author = {Herrup, K.},
title = {{Reimagining Alzheimer's disease--an age-based hypothesis}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2010},
doi = {10.1523/jneurosci.4521-10.2010},
pmid = {21159946},
url = {https://doi.org/10.1523/jneurosci.4521-10.2010}
}
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