Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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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 - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
JF - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
SN - 1530-6860
IS - 8
ER -