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

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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.

In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 24, No. 8, 2010, p. 2716-2726.

Research output: Contribution to journalJournal article

Harvard

Fukumoto, H, Tokuda, T, Kasai, T, Ishigami, N, Hidaka, H, Kondo, M, Allsop, D & Nakagawa, M 2010, 'High-molecular-weight β-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients', The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol. 24, no. 8, pp. 2716-2726. https://doi.org/10.1096/fj.09-150359

APA

Fukumoto, H., Tokuda, T., Kasai, T., Ishigami, N., Hidaka, H., Kondo, M., Allsop, D., & Nakagawa, M. (2010). High-molecular-weight β-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 24(8), 2716-2726. 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 β-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2010;24(8):2716-2726. https://doi.org/10.1096/fj.09-150359

Author

Fukumoto, Hiroaki ; Tokuda, Takahiko ; Kasai, Takashi ; Ishigami, Noriko ; Hidaka, Hiroya ; Kondo, Masaki ; Allsop, David ; Nakagawa, Masanori. / High-molecular-weight β-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients. In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2010 ; Vol. 24, No. 8. pp. 2716-2726.

Bibtex

@article{5c0bbfef1c114f2ba7b7d22c9215bb9f,
title = "High-molecular-weight β-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients",
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.",
keywords = "Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Biological Markers, Case-Control Studies, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Molecular Weight, Protein Multimerization",
author = "Hiroaki Fukumoto and Takahiko Tokuda and Takashi Kasai and Noriko Ishigami and Hiroya Hidaka and Masaki Kondo and David Allsop and Masanori Nakagawa",
year = "2010",
doi = "10.1096/fj.09-150359",
language = "English",
volume = "24",
pages = "2716--2726",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "8",

}

RIS

TY - JOUR

T1 - High-molecular-weight β-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients

AU - Fukumoto, Hiroaki

AU - Tokuda, Takahiko

AU - Kasai, Takashi

AU - Ishigami, Noriko

AU - Hidaka, Hiroya

AU - Kondo, Masaki

AU - Allsop, David

AU - Nakagawa, Masanori

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - Alzheimer Disease

KW - Amyloid beta-Peptides

KW - Biological Markers

KW - Case-Control Studies

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Molecular Weight

KW - Protein Multimerization

U2 - 10.1096/fj.09-150359

DO - 10.1096/fj.09-150359

M3 - Journal article

C2 - 20339023

VL - 24

SP - 2716

EP - 2726

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 8

ER -