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

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  • Hiroaki Fukumoto
  • Takahiko Tokuda
  • Takashi Kasai
  • Noriko Ishigami
  • Hiroya Hidaka
  • Masaki Kondo
  • David Allsop
  • Masanori Nakagawa
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<mark>Journal publication date</mark>2010
<mark>Journal</mark>The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Issue number8
Volume24
Number of pages11
Pages (from-to)2716-2726
Publication statusPublished
Original languageEnglish

Abstract

There is accumulating evidence that soluble amyloid-β (Aβ) 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) Aβ oligomers. Analysis of Aβ oligomers derived from synthetic Aβ1-42, by size-exclusion chromatography (SEC), revealed that our ELISA specifically detected HMW Aβ 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 Aβ oligomers was greater than that for CSF Aβx-42. Furthermore, the CSF levels of HMW Aβ oligomers showed a negative correlation with Mini-Mental State Examination scores in the AD/MCI group. We conclude that the CSF HMW Aβ 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 Aβ oligomers play a critical role in the pathogenesis and progression of AD.—Fukumoto, H., Tokuda, T., Kasai, T., Ishigami, N., Hidaka, H., Kondo, M., Allsop, D., Nakagawa, M. High-molecular weight β-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients.