A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease.
Much evidence indicates that abnormal processing and extracellular deposition of amyloid-beta peptide (A beta), a proteolytic derivative of the beta-amyloid precursor protein (betaAPP), is central to the pathogenesis of Alzheimer's disease (reviewed in ref. 1). In the PDAPP transgenic mouse model of Alzheimer's disease, immunization with A beta causes a marked reduction in burden of the brain amyloid. Evidence that A beta immunization also reduces cognitive dysfunction in murine models of Alzheimer's disease would support the hypothesis that abnormal A beta processing is essential to the pathogenesis of Alzheimer's disease, and would encourage the development of other strategies directed at the 'amyloid cascade'. Here we show that A beta immunization reduces both deposition of cerebral fibrillar A beta and cognitive dysfunction in the TgCRND8 murine model of Alzheimer's disease without, however, altering total levels of A beta in the brain. This implies that either a approximately 50% reduction in dense-cored A beta plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic A beta species.
Janus
C
C
Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Ontario, Canada.
Pearson
J
J
McLaurin
J
J
Mathews
P M
PM
Jiang
Y
Y
Schmidt
S D
SD
Chishti
M A
MA
Horne
P
P
Heslin
D
D
French
J
J
Mount
H T
HT
Nixon
R A
RA
Mercken
M
M
Bergeron
C
C
Fraser
P E
PE
St George-Hyslop
P
P
Westaway
D
D
D000544:Alzheimer Disease / Q000473:pathology / Q000517:prevention & control*; D000682:Amyloid / Q000008:administration & dosage; D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D006224:Cricetinae; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D058228:Islet Amyloid Polypeptide; D018782:Maze Learning; D008647:Mesocricetus; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage*; D058225:Plaque, Amyloid; D014611:Vaccination
D000682:Amyloid; D016229:Amyloid beta-Peptides; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)