Topic: Amyloid, tau and blood-test diagnosis
Genetic and environmental factors that increase the risk of late-onset Alzheimer disease are now well recognized but the cause of variable progression rates and phenotypes of sporadic Alzheimer's disease is largely unknown. We aimed to investigate the relationship between diverse structural assemblies of amyloid-β and rates of clinical decline in Alzheimer's disease. Using novel biophysical methods, we analysed levels, particle size, and conformational characteristics of amyloid-β in the posterior cingulate cortex, hippocampus and cerebellum of 48 cases of Alzheimer's disease with distinctly different disease durations, and correlated the data with APOE gene polymorphism. In both hippocampus and posterior cingulate cortex we identified an extensive array of distinct amyloid-β42 particles that differ in size, display of N-terminal and C-terminal domains, and conformational stability. In contrast, amyloid-β40 present at low levels did not form a major particle with discernible size, and both N-terminal and C- terminal domains were largely exposed. Rapidly progressive Alzheimer's disease that is associated with a low frequency of APOE e4 allele demonstrates considerably expanded conformational heterogeneity of amyloid-β42, with higher levels of distinctly structured amyloid-β42 particles composed of 30-100 monomers, and fewer particles composed of < 30 monomers. The link between rapid clinical decline and levels of amyloid-β42 with distinct structural characteristics suggests that different conformers may play an important role in the pathogenesis of distinct Alzheimer's disease phenotypes. These findings indicate that Alzheimer's disease exhibits a wide spectrum of amyloid-β42 structural states and imply the existence of prion-like conformational strains.
Key findings
- Rapidly progressive Alzheimer's disease that is associated with a low frequency of APOE e4 allele demonstrates considerably expanded conformational heterogeneity of amyloid-β42, with higher levels of distinctly structured amyloid-β42 particles composed of 30-100 monomers, and fewer particles composed of < 30 monomers.
- The link between rapid clinical decline and levels of amyloid-β42 with distinct structural characteristics suggests that different conformers may play an important role in the pathogenesis of distinct Alzheimer's disease phenotypes.
- These findings indicate that Alzheimer's disease exhibits a wide spectrum of amyloid-β42 structural states and imply the existence of prion-like conformational strains.
Why it matters
In brain tissue from 48 Alzheimer disease cases, rapidly progressive disease associated with a low frequency of APOE epsilon4 showed more varied structures of amyloid-beta42 particles. This links different amyloid-beta structures to rates of clinical decline but does not test a treatment or cure.
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Study details
- Evidence strengthLow
How this study scored 62/100
Published in a leading specialty journal, and it is a randomised controlled trial. Scored zero for sample size and effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| 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 | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 5 / 7 | Cited 205 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.8 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 14.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 39 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Jiri Safar: h-index 51 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Case Western Reserve University: institution h-index 1,159 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25688081) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 62 / 100 | — |
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Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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. 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.
APA 7th
Cohen, M. L., Kim, C., Haldiman, T., ElHag, M., Mehndiratta, P., Pichet, T., et al. (2015). Rapidly progressive Alzheimer's disease features distinct structures of amyloid-β. Brain : a journal of neurology. https://doi.org/10.1093/brain/awv006
Vancouver
Cohen ML, Kim C, Haldiman T, ElHag M, Mehndiratta P, Pichet T, et al. Rapidly progressive Alzheimer's disease features distinct structures of amyloid-β. Brain : a journal of neurology. 2015. doi:10.1093/brain/awv006. PMID: 25688081.
BibTeX
@article{cohen2015-25688081,
author = {Cohen, M. L. and Kim, C. and Haldiman, T. and ElHag, M. and Mehndiratta, P. and Pichet, T. and Lissemore, F. and Shea, M. and others},
title = {{Rapidly progressive Alzheimer's disease features distinct structures of amyloid-β}},
journal = {Brain : a journal of neurology},
year = {2015},
doi = {10.1093/brain/awv006},
pmid = {25688081},
url = {https://doi.org/10.1093/brain/awv006}
}
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