Quantification of modified amyloid β peptides in Alzheimer disease and Down syndrome brains

被引:77
作者
Hosoda, R
Saido, TC
Otvos, L
Arai, T
Mann, DMA
Lee, VMY
Trojanowski, JQ
Iwatsubo, T
机构
[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Neuropathol & Neurosci, Bunkyo Ku, Tokyo 1130033, Japan
[2] Sci Univ Tokyo, Fac Sci & Technol, Dept Appl Biol Sci, Noda, Chiba 278, Japan
[3] RIKEN, Brain Sci Inst, Lab Proteolyt Neurosci, Wako, Saitama 35101, Japan
[4] Wistar Inst, Philadelphia, PA 19104 USA
[5] Univ Manchester, Dept Pathol Sci, Manchester M13 9PL, Lancs, England
[6] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[7] Japan Sci & Technol Corp, CREST, Tokyo, Japan
关键词
Alzheimer disease; amyloid beta peptide; Down syndrome; enzyme-linked immunosorbent assay; modification; senile plaque;
D O I
10.1097/00005072-199811000-00012
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
To gain insights into the different forms of modified amyloid beta peptides (A beta) in the Alzheimer disease (AD) and Down syndrome (DS) brain, we used two-site ELISAs with antibodies specific for isomerized (i.e. A beta with L-isoaspartate at positions 1 and 7) and pyroglutamate-modified (i.e. A beta beginning with pyroglutamate at position 3) forms of A beta to quantitate the levels of these different A beta peptides in formic acid extracts of AD and DS frontal cortex. Despite variations in the proportions of distinct forms of A beta in AD and DS frontal cortex, the major species of A beta in these samples were A beta N3(pyroGlu)-42 as well as A beta x-42 (where x is a residue at position 2 or less in A beta), whereas isomerized A beta was a minor species. Further, the levels of isomerized and pyroglutamate-modified forms of A beta terminating at amino acid 42 were higher than those ending at amino acid 40. The abundance of the distinct forms of A beta reported here In formic acid extracts of AD and DS frontal cortex suggests that these A beta species could play important roles in the deposition of A beta in AD and DS brains.
引用
收藏
页码:1089 / 1095
页数:7
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