Dataset Information

A two-step immunoassay for the simultaneous assessment of A?38, A?40 and A?42 in human blood plasma supports the A?42/A?40 ratio as a promising biomarker candidate of Alzheimer's disease.

ABSTRACT:

Background

The quantification of amyloid-beta (A?) peptides in blood plasma as potential biomarkers of Alzheimer's disease (AD) is hampered by very low A? concentrations and the presence of matrix components that may interfere with the measurements.

Methods

We developed a two-step immunoassay for the simultaneous measurement of the relative levels of A?38, A?40 and A?42 in human EDTA plasma. The assay was employed for the study of 23 patients with dementia of the Alzheimer's type (AD-D) and 17 patients with dementia due to other reasons (OD). We examined relationships with the clinical diagnosis, cerebral A? load as quantified by amyloid-positron emission tomography, apolipoprotein E genotype, A? levels and Tau protein in cerebrospinal fluid.

Results

Preconcentration of plasma A? peptides by immunoprecipitation substantially facilitated their immunological measurements. The A?42/A?40 and A?42/A?38 ratios were statistically significantly lower in the AD-D patients than in the OD group. The areas under the receiver operating characteristic curves reached 0.87 for the A?42/A?40 ratio and 0.80 for the A?42/A?38 ratio.

Conclusions

The measurement of plasma A? peptides with an immunological assay can be improved by preconcentration via immunoprecipitation with an antibody against the A? amino-terminus and elution of the captured peptides by heating in a mild detergent-containing buffer. Our findings support the A?42/A?40 ratio in blood plasma as a promising AD biomarker candidate which correlates significantly with the validated core biomarkers of AD. Further studies will be needed for technical advancement of the assay and validation of the biomarker findings.

SUBMITTER: Shahpasand-Kroner H

PROVIDER: S-EPMC6286509 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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A two-step immunoassay for the simultaneous assessment of Aβ38, Aβ40 and Aβ42 in human blood plasma supports the Aβ42/Aβ40 ratio as a promising biomarker candidate of Alzheimer's disease.

Shahpasand-Kroner Hedieh H Klafki Hans-W HW Bauer Chris C Schuchhardt Johannes J Hüttenrauch Melanie M Stazi Martina M Bouter Caroline C Wirths Oliver O Vogelgsang Jonathan J Wiltfang Jens J

Alzheimer's research & therapy 20181208 1

<h4>Background</h4>The quantification of amyloid-beta (Aβ) peptides in blood plasma as potential biomarkers of Alzheimer's disease (AD) is hampered by very low Aβ concentrations and the presence of matrix components that may interfere with the measurements.<h4>Methods</h4>We developed a two-step immunoassay for the simultaneous measurement of the relative levels of Aβ38, Aβ40 and Aβ42 in human EDTA plasma. The assay was employed for the study of 23 patients with dementia of the Alzheimer's type ...[more]

PMID: 30526652

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