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

Abstract

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). We invented a novel sequential aminoterminally and carboxyterminally specific immunoprecipitation protocol and used the Aβ-SDS-PAGE/immunoblot for subsequent analysis of CSF Aβ peptide patterns. 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 1-38(ox), 2-40, and 2-42 in addition to the well known panel of Aβ 1-37, 1-38, 1-39, 1-40, 1-40(ox), and 1-42 in a group of seven patients with peripheral polyneuropathy. 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, 1-40(ox), and 1-42) by Aβ 1-38(ox), 2-40, and 2-42. An exact analysis of CSF Aβ peptides regarding their carboxy- and aminoterminus as well as posttranslational modification seems promising with respect to diagnostic and pathogenic aspects.