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- Title
High-molecular-weight β-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients.
- Authors
Fukumoto, Hiroaki; Tokuda, Takahiko; Kasai, Takashi; Ishigami, Noriko; Hidaka, Hiroya; Kondo, Masaki; Allsop, David; Nakagawa, Masanori
- 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.
- Subjects
AMYLOID beta-protein; OLIGOMERS; ALZHEIMER'S disease; ENZYME-linked immunosorbent assay; MOLECULAR weights; CEREBROSPINAL fluid
- Publication
FASEB Journal, 2010, Vol 24, Issue 8, p2716
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.09-150359