Highly conserved and disease-specific patterns of carboxyterminally truncated Aβ peptides 1-37/38/39 in addition to 1-40/42 in Alzheimer's disease and in patients with chronic neuroinflammation

被引:235
作者
Wiltfang, J
Esselmann, H
Bibl, M
Smirnov, A
Otto, M
Paul, S
Schmidt, B
Klafki, HW
Maler, M
Dyrks, T
Bienert, M
Beyermann, M
Rüther, E
Kornhuber, J
机构
[1] Univ Gottingen, Dept Psychiat, D-37075 Gottingen, Germany
[2] Univ Gottingen, Dept Neurol, D-37075 Gottingen, Germany
[3] Univ Gottingen, Dept Biochem 2, D-37075 Gottingen, Germany
[4] NADAG, Munich, Germany
[5] Univ Erlangen Nurnberg, Dept Psychiat, Erlangen, Germany
[6] Schering AG, CNS Res, D-1000 Berlin, Germany
[7] Res Inst Mol Pharmacol, Berlin, Germany
关键词
Alzheimer's disease (AD); beta-amyloid protein precursor/metabolism; biological markers; cerebrospinal fluid; 2D-PAGE; western immunoblot;
D O I
10.1046/j.1471-4159.2002.00818.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human lumbar CSF patterns of Abeta peptides were analysed by urea-based beta-amyloid sodium dodecyl sulphate polyacrylamide gel electrophoresis with western immunoblot (Abeta-SDS-PAGE/immunoblot). A highly conserved pattern of carboxyterminally truncated Abeta1-37/38/39 was found in addition to Abeta1-40 and Abeta1-42. Remarkably, Abeta1-38 was present at a higher concentration than Abeta1-42, being the second prominent Abeta peptide species in CSF. Patients with Alzheimer's disease (AD, n = 12) and patients with chronic inflammatory CNS disease (CID, n = 10) were differentiated by unique CSF Abeta peptide patterns from patients with other neuropsychiatric diseases (OND, n = 37). This became evident only when we investigated the amount of Abeta peptides relative to their total Abeta peptide concentration (Abeta1-x%, fractional Abeta peptide pattern), which may reflect disease-specific gamma-secretase activities. Remarkably, patients with AD and CID shared elevated Abeta1-38% values, whereas otherwise the patterns were distinct, allowing separation of AD from CID or OND patients without overlap. The presence of one or two ApoE epsilon4 alleles resulted in an overall reduction of CSF Abeta peptides, which was pronounced for Abeta1-42. The severity of dementia was significantly correlated to the fractional Abeta peptide pattern but not to the absolute Abeta peptide concentrations.
引用
收藏
页码:481 / 496
页数:16
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