Intravenous immunoglobulins containing antibodies against β-amyloid for the treatment of Alzheimer's disease

被引:264
作者
Dodel, RC
Du, Y
Depboylu, C
Hampel, H
Frölich, L
Haag, A
Hemmeter, U
Paulsen, S
Teipel, SJ
Brettschneider, S
Spottke, A
Nölker, C
Möller, HJ
Wei, X
Farlow, M
Sommer, N
Oertel, WH
机构
[1] Univ Bonn, Dept Neurol, D-53105 Bonn, Germany
[2] Indiana Univ, Dept Neurol, Indianapolis, IN 46204 USA
[3] Univ Munich, Dept Psychiat, D-8000 Munich, Germany
[4] Univ Frankfurt, Dept Psychiat, Frankfurt, Germany
[5] Univ Marburg, Dept Neurol, D-35032 Marburg, Germany
[6] Univ Marburg, Dept Psychiat, D-35032 Marburg, Germany
关键词
D O I
10.1136/jnnp.2003.033399
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: Active or passive immunisation can mitigate plaque pathology in murine models of Alzheimer's disease (AD). Recently, it has been shown that antibodies against β-amyloid (Aβ) are present in human immunoglobulin preparations (IVIgG), which specifically recognise and inhibit the neurotoxic effects of Aβ. This study reports the results from a pilot study using IVIgG in patients with AD. Methods: Five patients with AD were enrolled and received monthly IVIgG over a 6 month period. Efficacy assessment included total Aβ/Aβ1-42 measured in the CSF/serum as well as effects on cognition (ADAS-cog; CERAD) at baseline and at 6 months following IVIgG. Results: Following IVIgG, total Aβ levels in the CSF decreased by 30.1% (17.3-43.5%) compared to baseline (p<0.05). Total Aβ increased in the serum by 233% (p<0.05). No significant change was found in Aβ1-42 levels in the CSF/serum. Using ADAS-cog, an improvement of 3.7±2.9 points was detected. Scores in the MMSE were essentially unchanged (improved in four patients, stable in one patient) following IVIgG compared to baseline. Conclusion: Although the sample size of this pilot study is too small to draw a clear conclusion, the results of this pilot study provide evidence for a more detailed investigation of IVIgG for the treatment of AD.
引用
收藏
页码:1472 / 1474
页数:3
相关论文
共 15 条
[11]  
MCKHANN G, 1984, NEUROLOGY, V34, P939, DOI 10.1212/WNL.34.7.939
[12]   Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease [J].
Morgan, D ;
Diamond, DM ;
Gottschall, PE ;
Ugen, KE ;
Dickey, C ;
Hardy, J ;
Duff, K ;
Jantzen, P ;
DiCarlo, G ;
Wilcock, D ;
Connor, K ;
Hatcher, J ;
Hope, C ;
Gordon, M ;
Arendash, GW .
NATURE, 2000, 408 (6815) :982-985
[13]   Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide:: a case report [J].
Nicoll, JAR ;
Wilkinson, D ;
Holmes, C ;
Steart, P ;
Markham, H ;
Weller, RO .
NATURE MEDICINE, 2003, 9 (04) :448-452
[14]   Immunization with amyloid-β attenuates Alzheimer disease-like pathology in the PDAPP mouse [J].
Schenk, D ;
Barbour, R ;
Dunn, W ;
Gordon, G ;
Grajeda, H ;
Guido, T ;
Hu, K ;
Huang, JP ;
Johnson-Wood, K ;
Khan, K ;
Kholodenko, D ;
Lee, M ;
Liao, ZM ;
Lieberburg, I ;
Motter, R ;
Mutter, L ;
Soriano, F ;
Shopp, G ;
Vasquez, N ;
Vandevert, C ;
Walker, S ;
Wogulis, M ;
Yednock, T ;
Games, D ;
Seubert, P .
NATURE, 1999, 400 (6740) :173-177
[15]   Increased incidence of anti-beta-amyloid autoantibodies secreted by Epstein-Barr virus transformed B cell lines from patients with Alzheimer's disease [J].
Xu, SH ;
Gaskin, F .
MECHANISMS OF AGEING AND DEVELOPMENT, 1997, 94 (1-3) :213-222