CORRELATIVE MEMORY DEFICITS, A-BETA ELEVATION, AND AMYLOID PLAQUES INTRANSGENIC MICE

Transgenic mice overexpressing the 695-amino acid isoform of human Alz heimer beta-amyloid (A beta) precursor protein containing a Lys(670) - -> Asn, Met(671)--> Leu mutation had normal learning and memory in spa tial reference and alternation tasks at 3 months of age but showed imp airment by 9 to 10 months of age. A fivefold increase in A beta(1-40) and a 14-fold increase in A beta(1-42/43) accompanied the appearance o f these behavioral deficits, Numerous A beta plaques that stained with Congo red dye were present in cortical and limbic structures of mice with elevated amounts of A beta. The correlative appearance of behavio ral, biochemical, and pathological abnormalities reminiscent of Alzhei mer's disease in these transgenic mice suggests new opportunities for exploring the pathophysiology and neurobiology of this disease.