Aminoterminally Truncated and Oxidized Amyloid-β Peptides in the Cerebrospinal Fluid of Alzheimer's Disease Patients

: Carboxyterminally elongated and aminoterminally truncated amyloid-β (Aβ) peptides and their oxidized derivates are major constituents of human amyloid plaques. The objective of the present study was to clarify the diagnostic impact of the Aβ peptides 1-38ox, 2-40, and 2-42 peptides on the neurochemical cerebrospinal fluid (CSF) diagnosis of Alzheimer's disease (AD). For this purpose, 22 patients with AD and 20 non-demented disease controls (NDC) were comparatively analyzed for their cerebrospinal fluid pattern of Aβ1-38ox, Aβ2-40, and Aβ2-42 along with Aβ1-37, Aβ1-38, Aβ1-39, Aβ1-40, Aβ1-40ox, and Aβ1-42 using a novel sequential aminoterminally and carboxyterminally specific immunoprecipitation protocol and subsequent analysis in the Aβ-SDS-PAGE/immunoblot. The Aβ peptides 1-38ox, 2-40, and 2-42 could not be consistently detected in the investigated CSF samples, which applied to samples from AD and NDC patients alike. Otherwise, our approach revealed a striking decrease of Aβ1-42 and Aβ2-42, but not of Aβ1-38ox and Aβ2-40 in AD. Both Aβ1-42 and Aβ2-42 reached reasonable accuracies for diagnosing AD alone as well as in relation to Aβ1-40, Aβ1-38, or the sum of all measured Aβ peptides. Aβ1-38ox was negatively correlated to the Mini-Mental Status Examination score of AD patients, indicating that this peptide to linked to disease severity. We conclude that an exact analysis of CSF Aβ peptides regarding their carboxy- and aminoterminus as well as posttranslational modification may be a promising approach for diagnosing and tracking AD.