Decreased serum amyloid β1-42 autoantibody levels in Alzheimer's disease, determined by a newly developed immuno-precipitation assay with radiolabeled amyloid β1-42 peptide

被引:62
作者
Brettschneider, S
Morgenthaler, NG
Teipel, SJ
Fischer-Schulz, C
Bürger, K
Dodel, R
Du, YS
Möller, HJ
Bergmann, A
Hampel, H
机构
[1] Univ Munich, Dept Psychiat, Alzheimer Mem Ctr, D-80336 Munich, Germany
[2] Univ Munich, Dept Psychiat, Geriatr Psychiat Branch, D-80336 Munich, Germany
[3] Univ Munich, Dept Psychiat, Dementia Res Sect, D-80336 Munich, Germany
[4] Univ Munich, Dept Psychiat, Memory Clin, D-80336 Munich, Germany
[5] BRAHMS AG, Ctr Biotechnol, Henningsdorf Berlin, Germany
[6] Univ Bonn, Dept Neurol, D-5300 Bonn, Germany
[7] Indiana Univ, Sch Med, Dept Neurol, Indianapolis, IN 46204 USA
关键词
Alzheimer's disease; A beta autoantibodies; biomarkers; cerebrospinal fluid (CSF); diagnosis; bioassay;
D O I
10.1016/j.biopsych.2004.12.008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: Autoantibodies against amyloid beta (A beta) peptide found in patients with Alzheimer's disease (AD) also occur naturally in the general population independently of the cognitive status. Methods: We compared serum A beta(1-42) autoantibody levels (A beta(1-42)-AL) of 96 AD patients and 30 healthy elderly control subjects (HC), assessing their diagnostic value for AD with a newly developed immunoprecipitation assaywith radiolabeled A beta(1-42) peptide. Results: We found a highly significant decrease of A beta(1-42)-AL in AD patients (p =.001) independently of age, cognitive status, and apolipoprotein E epsilon 4 carrier status. Amyloid beta(1-42) autoantibody levels were correlated with gender in AD, with a higher level occurring in women. When A beta(1-42) autoantibody sensitivity (specificity) was set > 80%, specificity (sensitivity) was below 50% to correctly allocate patients and healthy control subjects. Conclusions: Our data indicate a potentially pathophysiologic decrease of serum. A beta(1-42) antibodies in AD. Amyloid beta(1-42) antibodies in the serum alone, however, seem not to be useful as a diagnostic marker of AD.
引用
收藏
页码:813 / 816
页数:4
相关论文
共 24 条
[1]  
Alzheimers Assoc, 1998, NEUROBIOL AGING, V19, P109
[2]   Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease [J].
Bard, F ;
Cannon, C ;
Barbour, R ;
Burke, RL ;
Games, D ;
Grajeda, H ;
Guido, T ;
Hu, K ;
Huang, JP ;
Johnson-Wood, K ;
Khan, K ;
Kholodenko, D ;
Lee, M ;
Lieberburg, I ;
Motter, R ;
Nguyen, M ;
Soriano, F ;
Vasquez, N ;
Weiss, K ;
Welch, B ;
Seubert, P ;
Schenk, D ;
Yednock, T .
NATURE MEDICINE, 2000, 6 (08) :916-919
[3]   Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231 [J].
Buerger, K ;
Zinkowski, R ;
Teipel, SJ ;
Tapiola, T ;
Arai, H ;
Blennow, K ;
Andreasen, N ;
Hofmann-Kiefer, K ;
DeBernardis, J ;
Kerkman, D ;
McCulloch, C ;
Kohnken, R ;
Padberg, F ;
Pirttilä, T ;
Schapiro, MB ;
Rapoport, SI ;
Möller, HJ ;
Davies, P ;
Hampel, H .
ARCHIVES OF NEUROLOGY, 2002, 59 (08) :1267-1272
[4]   Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's disease [J].
DeMattos, RB ;
Bales, KR ;
Cummins, DJ ;
Dodart, JC ;
Paul, SM ;
Holtzman, DM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (15) :8850-8855
[5]   Plaque-associated disruption of CSF and plasma amyloid-β (Aβ) equilibrium in a mouse model of Alzheimer's disease [J].
DeMattos, RB ;
Bales, KR ;
Parsadanian, M ;
O'Dell, MA ;
Foss, EM ;
Paul, SM ;
Holtzman, DM .
JOURNAL OF NEUROCHEMISTRY, 2002, 81 (02) :229-236
[6]   Human antibodies against amyloid β peptide:: A potential treatment for Alzheimer's disease [J].
Dodel, R ;
Hampel, H ;
Depboylu, C ;
Lin, SZ ;
Gao, F ;
Shock, S ;
Jäckel, S ;
Wei, W ;
Buerger, K ;
Höft, C ;
Hemmer, B ;
Möller, HJ ;
Farlow, M ;
Oertel, WH ;
Sommer, N ;
Du, YS .
ANNALS OF NEUROLOGY, 2002, 52 (02) :253-256
[7]   Immunotherapy for Alzheimer's disease [J].
Dodel, RC ;
Hampel, H ;
Du, YS .
LANCET NEUROLOGY, 2003, 2 (04) :215-220
[8]   Reduced levels of amyloid β-peptide antibody in Alzheimer disease [J].
Du, Y ;
Dodel, R ;
Hampel, H ;
Buerger, K ;
Lin, S ;
Eastwood, B ;
Bales, K ;
Gao, F ;
Moeller, HJ ;
Oertel, W ;
Farlow, M ;
Paul, S .
NEUROLOGY, 2001, 57 (05) :801-805
[9]   Human anti-β-amyloid antibodies block β-amyloid fibril formation and prevent β-amyloid-induced neurotoxicity [J].
Du, YS ;
Wei, X ;
Dodel, R ;
Sommer, N ;
Hampel, H ;
Gao, F ;
Ma, ZZ ;
Zhao, LM ;
Oertel, WH ;
Farlow, M .
BRAIN, 2003, 126 :1935-1939
[10]   HUMAN-ANTIBODIES REACTIVE WITH BETA-AMYLOID PROTEIN IN ALZHEIMERS-DISEASE [J].
GASKIN, F ;
FINLEY, J ;
FANG, Q ;
XU, SH ;
FU, SM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 177 (04) :1181-1186