Short-term β-amyloid vaccinations do not improve cognitive performance in cognitively impaired APP+PS1 mice

被引:32
作者
Austin, L
Arendash, GW
Gordon, MN
Diamond, DM
DiCarlo, G
Dickey, C
Ugen, K
Morgan, D
机构
[1] Univ S Florida, Memory & Aging Res Lab, Tampa, FL 33620 USA
[2] Univ S Florida, Dept Biol, Tampa, FL 33620 USA
[3] Univ S Florida, Dept Pharmacol, Tampa, FL 33620 USA
[4] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA
[5] Univ S Florida, Dept Microbiol, Tampa, FL 33620 USA
关键词
D O I
10.1037/0735-7044.117.3.478
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Prior work demonstrated that beta-amyloid (Abeta) immunotherapy for 8 months prevented cognitive impairment in 16-month-old APP+PS1 transgenic mice. In the present study, 4 immunizations administered biweekly to cognitively impaired 16-month-old transgenic mice could not reverse deficits in working memory or reference memory in the radial arm water maze or in visual platform recognition, possibly because of inadequate antibody exposure. Nontransgenic mice showed cognitive savings between the 16-and 18-month test periods, but the transgenic groups did not. These results suggest that a longer period of active immunotherapy, or passive immunization, may be required to provide sufficient antibody titers to improve cognition in older transgenic mice. Abeta-based immunotherapy for Alzheimer's disease will likely be more successful prophylactically than therapeutically.
引用
收藏
页码:478 / 484
页数:7
相关论文
共 23 条
[1]   Intra- and intertask relationships in a behavioral test battery given to Tg2576 transgenic mice and controls [J].
Arendash, GW ;
King, DL .
PHYSIOLOGY & BEHAVIOR, 2002, 75 (05) :643-652
[2]   Behavioral assessment of Alzheimer's transgenic mice following long-term Aβ vaccination:: Task specificity and correlations between Aβ deposition and spatial memory [J].
Arendash, GW ;
Gordon, MN ;
Diamond, DM ;
Austin, LA ;
Hatcher, JM ;
Jantzen, P ;
Dicarlo, G ;
Wilcock, D ;
Morgan, D .
DNA AND CELL BIOLOGY, 2001, 20 (11) :737-744
[3]   Progressive, age-related behavioral impairments in transgenic mice carrying both mutant amyloid precursor protein and presenilin-1 transgenes [J].
Arendash, GW ;
King, DL ;
Gordon, MN ;
Morgan, D ;
Hatcher, JM ;
Hope, CE ;
Diamond, DM .
BRAIN RESEARCH, 2001, 891 (1-2) :42-53
[4]   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
[5]   A BEHAVIORAL-ANALYSIS OF RATS WITH DAMAGE TO THE MEDIAL PREFRONTAL CORTEX USING THE MORRIS WATER MAZE - EVIDENCE FOR BEHAVIORAL FLEXIBILITY, BUT NOT FOR IMPAIRED SPATIAL NAVIGATION [J].
DEBRUIN, JPC ;
SANCHEZSANTED, F ;
HEINSBROEK, RPW ;
DONKER, A ;
POSTMES, P .
BRAIN RESEARCH, 1994, 652 (02) :323-333
[6]   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
[7]   Duration and specificity of humoral immune responses in mice vaccinated with the Alzheimer's disease-associated β-amyloid 1-42 peptide [J].
Dickey, CA ;
Morgan, DG ;
Kudchodkar, S ;
Weiner, DB ;
Bai, Y ;
Cao, CH ;
Gordon, MN ;
Ugen, KE .
DNA AND CELL BIOLOGY, 2001, 20 (11) :723-729
[8]   Immunization reverses memory deficits without reducing brain Aβ burden in Alzheimer's disease model [J].
Dodart, JC ;
Bales, KR ;
Gannon, KS ;
Greene, SJ ;
DeMattos, RB ;
Mathis, C ;
DeLong, CA ;
Wu, S ;
Wu, X ;
Holtzman, DM ;
Paul, SM .
NATURE NEUROSCIENCE, 2002, 5 (05) :452-457
[9]   Correlation between cognitive deficits and Aβ deposits in transgenic APP+PS1 mice [J].
Gordon, MN ;
King, DL ;
Diamond, DM ;
Jantzen, PT ;
Boyett, KV ;
Hope, CE ;
Hatcher, JM ;
DiCarlo, G ;
Gottschall, WPE ;
Morgan, D ;
Arendash, GW .
NEUROBIOLOGY OF AGING, 2001, 22 (03) :377-385
[10]   Amyloid, the presenilins and Alzheimer's disease [J].
Hardy, J .
TRENDS IN NEUROSCIENCES, 1997, 20 (04) :154-159