Alzheimer’s dementia (AD) and frontotemporal dementias (FTD) are common and their clinical differential diagnosis may be complicated by overlapping symptoms, which is why biomarkers may have an important role to play. Cerebrospinal fluids (CSF) Aβ2-42 and 1-42 have been shown to be similarly decreased in AD, but 1-42 did not display sufficient specificity for exclusion of other dementias from AD. The objective of the present study was to clarify the diagnostic value of Aβ2-42 peptides for the differential diagnosis of AD from FTD. For this purpose, 20 non-demented disease controls (NDC), 22 patients with AD and 17 with FTD were comparatively analysed by a novel sequential aminoterminally and carboxyterminally specific immunoprecipitation protocol with subsequent Aβ-SDS-PAGE/immunoblot, allowing the quantification of peptides 1-38ox, 2-40 and 2-42 along with Aβ 1-37, 1-38, 1-39, 1-40, 1-40ox and 1-42. CSF Aβ1-42 was decreased in AD as compared to NDC, but not to FTD. In a subgroup of the patients analyzed, the decrease of Abeta2-42 in AD was evident as compared to both NDC and FTD. Aβ1-38 was decreased in FTD as compared to NDC and AD. For differentiating AD from FTD, Aβ1-42 demonstrated sufficient diagnostic accuracies only when combined with Aβ1-38. Aβ2-42 yielded diagnostic accuracies of over 85 % as a single marker. These accuracy figures could be improved by combining Aβ2-42 to Aβ1-38. Aβ2-42 seems to be a promising biomarker for differentiating AD from other degenerative dementias, such as FTD.
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.
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.
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