Short-term beta-amyloid vaccinations do not improve cognitive performance in cognitively impaired APP + PS1 mice.
Prior work demonstrated that beta-amyloid (A beta) 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. A beta-based immunotherapy for Alzheimer's disease will likely be more successful prophylactically than therapeutically.
Austin
L
L
Department of Biology and Memory, Aging Research Laboratory, University of South Florida, Tampa, Florida, USA.
Arendash
G W
GW
Gordon
M N
MN
Diamond
D M
DM
DiCarlo
G
G
Dickey
C
C
Ugen
K
K
Morgan
D
D
D016229:Amyloid beta-Peptides / Q000627:therapeutic use*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003072:Cognition Disorders / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053764:Presenilin-1; D014611:Vaccination / Q000379:methods*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1