Antibody to Amyloid β Protein Alleviates Impaired Acquisition, Retention, and Memory Processing in SAMP8 Mice

Abstract

SAMP8 (senescence-accelerated mouse, P8 strain) mice overproduce amyloid precursor protein and β-amyloid and have learning and memory deficits. Preliminary data have indicated that overproduction of β-amyloid plays a role in the pathogenesis of acquisition and retention deficits in SAMP8 mice. In the studies reported here, the authors examined the effects of polyclonal and monoclonal antibodies to β-amyloid on acquisition and retention in an aversive T-maze testing paradigm when injected intracerebroventricularly (ICV) into 12-month SAMP8/TaJF mice. Both the polyclonal and monoclonal antibodies improved acquisition and retention when injected ICV 1 to 14 days prior to acquisition testing. Injection of all three antibodies intrahippocampally immediately following training improved retention on the T-maze when mice were tested 7 days later. The authors next studied the effect of monoclonal β-amyloid antibody injected 48 h prior to training on the effect on retention in the T-maze of drugs modulating classical neurotransmitters. Arecoline and glutamate were injected directly into the hippocampus, and ketanserin, methiothepen, bicuculline, and OH-saclofen were injected into the septum. Previously, the authors have found that the doses of these drugs required to improve retention are markedly altered in 12-month SAMP8/TkJF mice compared to 4-month P8 mice. In these studies, it was demonstrated that antibody to β-amyloid resulted in these drugs improving retention at doses that improved memory in 4-month SAMP8/TaJF mice. Based on these findings, we conclude that β-amyloid overproduction is at least in part responsible for the acquisition and memory deficits in 12-month-old SAMP8/TaJF mice. Antibody to β-amyloid restores the retention response to neurotransmitter manipulation to that seen in 4-month-old mice. β-amyloid appears to play a key role in the loss of acquisition and retention seen in SAMP8/TaJF mice.