Behavioral and neurochemical characterization of transgenic mice carrying the human presenilin-1 gene with or without the leucine-to-proline mutation at codon 235.
Human presenilin-1 (PS1) mutations are associated with the incidence of familial Alzheimer's disease. The present study evaluated the behavioral and neurochemical effects of the L235P mutation (substitution of leucine by proline at codon 235) of the human PS1 gene, which has been linked to a form of early-onset Alzheimer's disease. Except for a significant increase in the production of beta-amyloid-42, the mutant mice did not show any overt signs of Alzheimer-like neuropathology in the form of plaque formation, changes in choline acetyltransferase activity, or somatostatin content in the brain. Cognitive assays indicated that the mutation did not affect the acquisition or reversal of a spatial reference memory task in the water maze or performance on a spatial working memory task. In contrast, L235P PS1 transgenic mice exhibited a significant impairment in a test of spontaneous object recognition. This dissociation is suggestive of a preferential impairment of the extrahippocampal memory system and is consistent with what has been reported in another pathological mutation (substitution of leucine by valine at codon 286) of the PS1 gene.
Huang
X G
XG
Department of Physiology, Faculty of Medicine, University of Hong Kong, 21 Sassoon Road, Hong Kong, People's Republic of China.
Yee
B K
BK
Nag
S
S
Chan
S T H
ST
Tang
F
F
D000544:Alzheimer Disease / Q000235:genetics*; D019943:Amino Acid Substitution; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D018782:Maze Learning; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010446:Peptide Fragments / Q000096:biosynthesis; D053764:Presenilin-1; D021641:Recognition, Psychology; D013004:Somatostatin / Q000378:metabolism
D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D013004:Somatostatin; D002795:Choline O-Acetyltransferase