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Why Alzheimer trials fail: removing soluble oligomeric beta amyloid is essential, inconsistent, and difficult
Rosenblum WI.. Neurobiology of aging, 2013-10-19
Topic: Amyloid, tau and blood-test diagnosis
Before amyloid formation, peptides cleaved from the amyloid precursor protein (APP) exist as soluble oligomers. Their concentration is strongly correlated with synaptic impairment in animals and parallel cognitive decline in animals and humans. Clinical trials have largely been aimed at removing insoluble beta amyloid in senile plaques and have not reduced soluble load.
Key findings
- Their concentration is strongly correlated with synaptic impairment in animals and parallel cognitive decline in animals and humans.
- Clinical trials have largely been aimed at removing insoluble beta amyloid in senile plaques and have not reduced soluble load.
- Even treatment that should remove soluble oligomers has not consistently reduced the load.
- Failure to significantly improve cognition has frequently been attributed to failure of the amyloid hypothesis or to irreversible alteration in the brain.
Why it matters
This paper argues that clinical trials have largely aimed at removing insoluble beta amyloid in senile plaques and have not reduced soluble oligomer load, and that even treatments expected to remove soluble oligomers have not consistently done so. It concludes that failure to improve cognition has often been attributed to failure of the amyloid hypothesis or irreversible changes, not that a successful therapy has been found.
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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 randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of aging) |
| Journal's citation record | 3 / 4 | Neurobiology of Aging: journal h-index 263 (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 | 1 / 5 | 2014 — 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 | 5 / 7 | Cited 135 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.6 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 4 / 6 | Cited 9.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 1 / 4 | Cited 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author William I. Rosenblum: h-index 41 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Icahn School of Medicine at Mount Sinai: institution h-index 1,331 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24210593) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 43 / 100 | — |
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Read the original
May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.
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
Rosenblum, W. I. (2014). Why Alzheimer trials fail: removing soluble oligomeric beta amyloid is essential, inconsistent, and difficult. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2013.10.085
Vancouver
Rosenblum WI. Why Alzheimer trials fail: removing soluble oligomeric beta amyloid is essential, inconsistent, and difficult. Neurobiology of aging. 2014. doi:10.1016/j.neurobiolaging.2013.10.085. PMID: 24210593.
BibTeX
@article{rosenblum2014-24210593,
author = {Rosenblum, W. I.},
title = {{Why Alzheimer trials fail: removing soluble oligomeric beta amyloid is essential, inconsistent, and difficult}},
journal = {Neurobiology of aging},
year = {2014},
doi = {10.1016/j.neurobiolaging.2013.10.085},
pmid = {24210593},
url = {https://doi.org/10.1016/j.neurobiolaging.2013.10.085}
}
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