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

Purpose Carboxyterminally elongated and aminoterminally truncated A beta 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 A beta 38, A beta 40, and A beta 42 peptide species in immunoprecipitated human cerebrospinal fluid (CSF). Experimental design We invented a novel sequential aminoterminally and carboxyterminally specific immunoprecipitation protocol and used the A beta-SDS-PAGE/immunoblot for subsequent analysis of CSF A beta peptide patterns. Results In the present study, we identified the aminoterminally truncated A beta peptides 240 and 242 as well as oxidized forms of A beta 138 and A beta 142 in CSF. Our protocol allowed the quantification of a pattern of A beta peptides 138ox, 240, and 242 in addition to the well known panel of A beta 137, 138, 139, 140, 140ox, and 142 in a group of seven patients with peripheral polyneuropathy. Conclusions and clinical relevance In the present approach, we could broaden the range of quantifiable A beta peptides described in previous studies (i.e., 137, 138, 139, 140, 140ox, and 142) by A beta 138ox, 240, and 242. An exact analysis of CSF A beta peptides regarding their carboxy- and aminoterminus as well as posttranslational modification seems promising with respect to diagnostic and pathogenic aspects.