EPITOPE MAP OF 2 POLYCLONAL ANTIBODIES THAT RECOGNIZE AMYLOID LESIONS IN PATIENTS WITH ALZHEIMERS-DISEASE

被引:17
作者
GHISO, J [1 ]
WISNIEWSKI, T [1 ]
VIDAL, R [1 ]
ROSTAGNO, A [1 ]
FRANGIONE, B [1 ]
机构
[1] NYU MED CTR,DEPT NEUROL,NEW YORK,NY 10016
关键词
D O I
10.1042/bj2820517
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
Two synthetic peptides with sequences identical with those of fragments of the extracellular domain of the Alzheimer's-disease amyloid precursor protein (APP) were used to raise antibodies. SP28 comprises positions 597-624 of the APP695 isoform, whereas SP41 extends towards the N-terminus (amino acids 584-624) and contains the entire SP28 peptide. Using e.l.i.s.a. and inhibition experiments we identified the two beta-turn-containing segments 602-607 and 617-624 as the epitopes recognized by anti-SP41 and anti-SP28 respectively. Both antibodies immunolabelled amyloid lesions in brains from Alzheimer's-disease patients and patients with related disorders, whereas they were unreactive in control brains. However, when probed on immunoblots, anti-SP28 failed to detect full-length APP from baculovirus-infected Sf9 cells, and anti-SP41 reacted weakly compared with other anti-APP antisera. The data suggest that these antibodies are directed to conformational epitopes not existent in the native molecules but present after alternative APP processing.
引用
收藏
页码:517 / 522
页数:6
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