Inverse correlation between amyloid precursor protein and synaptic plasticity in transgenic mice

Soluble amyloid P peptide (A beta) is believed to cause synaptic dysfunction in the early stages of Alzheimer's disease. Here, we examined in-vivo synaptic functions in the hippocampus in two lines of transgenic mice expressing different amounts of human wild-type amyloid precursor protein (APP). Compared with non-transgenic littermates, one transgenic line with higher APP expression displayed potent inhibition of paired-pulse facilitation and long-term potentiation in the absence of amyloid deposition, whereas the line with lower APP expression exhibited moderate inhibition of paired-pulse facilitation and long-term potentiation. Soluble A beta I-42 levels in their brains nearly paralleled APP levels. The observed inverse correlation between APP expression and synaptic plasticity appears to support the current hypothesis regarding the pathogenic roles of soluble A beta.