Cited by 264Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

High‐molecular‐weight β‐amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients

Fukumoto, Hiroaki, Tokuda, Takahiko, Kasai, Takashi, Ishigami, Noriko, Hidaka, Hiroya, Kondo, Masaki, Allsop, David, Nakagawa, Masanori·2010·The FASEB Journal

Abstract

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.

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Crossref · 10.1096/fj.09-150359

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  • Nanotechnology-based immunoassays have established an Alzheimer's disease-dependent accumulation of oligomers in human cerebrospinal fluid.

    “These assays, which can be many orders of magnitude more sensitive than ELISAs, have established an AD-dependent accumulation of oligomers in human CSF (Fukumoto et al., 2010; Gao et al., 2010; Georganopoulou et al., 2005; Haes et al., 2005).”

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Authors
Fukumoto, H., Tokuda, T., Kasai, T., Ishigami, N., Hidaka, H., Kondo, M., Allsop, D., & Nakagawa, M.
Affiliations
  • Takeda (Japan) (JP)
  • Kyoto Prefectural University of Medicine (JP)
  • Shinshu University (JP)
  • Lancaster University (GB)
Corresponding author
Tokuda, Takahiko
Venue
The FASEB Journal
Publisher
Wiley
Published
2010-03-25
Volume
24
Issue
8
Pages
2716-2726
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
OpenAlex
W2152948641
Cited by
264
References
52
Citations by year
2026: 12 · 2025: 3 · 2024: 15 · 2023: 8 · 2022: 7 · 2021: 18 · 2020: 7 · 2019: 13 · 2018: 11 · 2017: 13 · 2016: 18 · 2015: 25 · 2014: 27 · 2013: 27 · 2012: 26
FWCI
18.82
Type
journal article
Language
en
Open access
closed
Locations
  • The FASEB Journal (publishedVersion)
  • PubMed (publishedVersion)
  • Lancaster EPrints (Lancaster University) (submittedVersion)
Funders
  • Ministry of Health, Labour and Welfare
  • Ministry of Education, Culture, Sports, Science and Technology (20591007)
  • Japan Society for the Promotion of Science
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
amyloid-beta oligomers, Alzheimer's disease, mild cognitive impairment, cerebrospinal fluid biomarkers, ELISA development, amyloid-beta 42, disease severity, diagnostic biomarkers, Mini-Mental State Examination
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Molecular Weight, Biomarkers, Case-Control Studies, Amyloid beta-Peptides, Protein Multimerization

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