Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice.
Transgenic mice overexpressing the 695-amino acid isoform of human Alzheimer beta-amyloid (Abeta) precursor protein containing a Lys670 --> Asn, Met671 --> Leu mutation had normal learning and memory in spatial reference and alternation tasks at 3 months of age but showed impairment by 9 to 10 months of age. A fivefold increase in Abeta(1-40) and a 14-fold increase in Abeta(1-42/43) accompanied the appearance of these behavioral deficits. Numerous Abeta plaques that stained with Congo red dye were present in cortical and limbic structures of mice with elevated amounts of Abeta. The correlative appearance of behavioral, biochemical, and pathological abnormalities reminiscent of Alzheimer's disease in these transgenic mice suggests new opportunities for exploring the pathophysiology and neurobiology of this disease.
Hsiao
K
K
Department of Neurology, UMHC Box 295, 420 Delaware Street, University of Minnesota, Minneapolis, MN 55455, USA.
Chapman
P
P
Nilsen
S
S
Eckman
C
C
Harigaya
Y
Y
Younkin
S
S
Yang
F
F
Cole
G
G
D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D016564:Amyloid beta-Protein Precursor / Q000032:analysis* / Q000235:genetics; D000818:Animals; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry; D007859:Learning Disabilities / Q000378:metabolism* / Q000473:pathology; D018782:Maze Learning; D008569:Memory Disorders / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000032:analysis*; D011597:Psychomotor Performance
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)