Characterization of cerebrospinal fluid aminoterminally truncated and oxidized amyloid-β peptides

Authors


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Correspondence: Professor Mirko Bibl, Department of Psychiatry, Psychotherapy and Addiction Medicine, Kliniken Essen-Mitte, University of Duisburg-Essen, Henricistrasse 92, Essen 45136, Germany

E-mail:m.bibl@kliniken-essen-mitte.de

Fax: +49-201-17430800

Abstract

Purpose

Carboxyterminally elongated and aminoterminally truncated Aβ peptides as well as their pyroglutamate and oxidized derivates are major constituents of human amyloid plaques. The objective of the present study was to characterize aminoterminally truncated or oxidized Aβ38, Aβ40, and Aβ42 peptide species in immunoprecipitated human cerebrospinal fluid (CSF).

Experimental design

We invented a novel sequential aminoterminally and carboxyterminally specific immunoprecipitation protocol and used the Aβ-SDS-PAGE/immunoblot for subsequent analysis of CSFAβ peptide patterns.

Results

In the present study, we identified the aminoterminally truncated Aβ peptides 2–40 and 2–42 as well as oxidized forms of Aβ1–38 and Aβ1–42 in CSF. Our protocol allowed the quantification of a pattern of Aβ peptides 1–38ox, 2–40, and 2–42 in addition to the well known panel of Aβ 1–37, 1–38, 1–39, 1–40, 1–40ox, and 1–42 in a group of seven patients with peripheral polyneuropathy.

Conclusions and clinical relevance

In the present approach, we could broaden the range of quantifiable Aβ peptides described in previous studies (i.e., 1–37, 1–38, 1–39, 1–40, 1–40ox, and 1–42) by Aβ 1–38ox, 2–40, and 2–42. An exact analysis of CSFAβ peptides regarding their carboxy- and aminoterminus as well as posttranslational modification seems promising with respect to diagnostic and pathogenic aspects.

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