Home › Research › Mild cognitive impairment
High-molecular-weight beta-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients
Fukumoto H, Tokuda T, Kasai T, Ishigami N, Hidaka H, Kondo M, Allsop D, Nakagawa M.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010-03-25
Topic: Amyloid, tau and blood-test diagnosis
There is accumulating evidence that soluble amyloid-beta (Abeta) oligomers, rather than amyloid fibrils, are the principal pathogenic species in Alzheimer disease (AD). Here, we have developed a novel enzyme-linked immunosorbent assay (ELISA) specific for high-molecular-weight (HMW) Abeta oligomers. Analysis of Abeta oligomers derived from synthetic Abeta 1-42, by size-exclusion chromatography (SEC), revealed that our ELISA specifically detected HMW Abeta oligomers of 40-200 kDa. Using this ELISA, we detected significantly higher (P<0.0001) signals in cerebrospinal fluid (CSF) samples from 25 patients with AD or mild cognitive impairment (MCI), compared to 25 age-matched controls. As a test for discriminating between the AD/MCI and control groups, the area under the curve in receiver operating characteristic analysis for the CSF HMW Abeta oligomers was greater than that for CSF Abeta x-42. Furthermore, the CSF levels of HMW Abeta oligomers showed a negative correlation with Mini-Mental State Examination scores in the AD/MCI group. We conclude that the CSF HMW Abeta oligomers detected by our ELISA could be useful as a diagnostic marker for AD, and also as a potential surrogate marker for disease severity. Our results support the idea that soluble HMW Abeta oligomers play a critical role in the pathogenesis and progression of AD.
Key findings
- Analysis of Abeta oligomers derived from synthetic Abeta 1-42, by size-exclusion chromatography (SEC), revealed that our ELISA specifically detected HMW Abeta oligomers of 40-200 kDa.
- Using this ELISA, we detected significantly higher (P<0.0001) signals in cerebrospinal fluid (CSF) samples from 25 patients with AD or mild cognitive impairment (MCI), compared to 25 age-matched controls.
- We conclude that the CSF HMW Abeta oligomers detected by our ELISA could be useful as a diagnostic marker for AD, and also as a potential surrogate marker for disease severity.
- Our results support the idea that soluble HMW Abeta oligomers play a critical role in the pathogenesis and progression of AD.
Why it matters
Using a new ELISA, higher levels of high-molecular-weight amyloid-β oligomers were detected in cerebrospinal fluid from 25 patients with Alzheimer's disease or mild cognitive impairment compared with 25 age-matched controls, and levels negatively correlated with Mini-Mental State Examination scores. The authors conclude these oligomers could be useful as a diagnostic marker and potential surrogate marker for disease severity, but no treatment was tested.
Study details
- Participants25
- Evidence strengthLow
How this study scored 49/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (FASEB journal : official publication of the Federation of American Societies for Experimental Biology) |
| Journal's citation record | 3 / 4 | The FASEB Journal: journal h-index 401 (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 | 2010 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 25 participants |
| 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 (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 265 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.7 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 4 / 6 | Cited 16.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 2 / 4 | Cited 31 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Masanori Nakagawa: h-index 57 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Lancaster University: institution h-index 694 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20339023) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 100 | — |
What each of these 20 components measures, and what this score is not →
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. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Fukumoto, H., Tokuda, T., Kasai, T., Ishigami, N., Hidaka, H., Kondo, M., et al. (2010). High-molecular-weight beta-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. https://doi.org/10.1096/fj.09-150359
Vancouver
Fukumoto H, Tokuda T, Kasai T, Ishigami N, Hidaka H, Kondo M, et al. High-molecular-weight beta-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2010. doi:10.1096/fj.09-150359. PMID: 20339023.
BibTeX
@article{fukumoto2010-20339023,
author = {Fukumoto, H. and Tokuda, T. and Kasai, T. and Ishigami, N. and Hidaka, H. and Kondo, M. and Allsop, D. and Nakagawa, M.},
title = {{High-molecular-weight beta-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients}},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
year = {2010},
doi = {10.1096/fj.09-150359},
pmid = {20339023},
url = {https://doi.org/10.1096/fj.09-150359}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
8 studies in the alzhub library list this one in their references.
Related studies in Mild cognitive impairment
Also tagged “amyloid-beta”
1,339 studies in the library carry the topic tag “amyloid-beta”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,339 tagged studies.