Transgenic mice over-expressing a mutated form of the human amyloid precursor 
protein (APP, 695 isoform) bearing a mutation associated with Alzheimer's 
disease (V642I, so-called London mutation, hereafter APPLd2) and wild-type 
controls were studied at age periods (3 and 10 months) prior to the overt 
development of neuritic amyloid plaques. Both 3- and 10-month-old APPLd2 mice 
had reflex eyelid responses like those of controls, but only younger mice were 
able to acquire a classical conditioning of eyelid responses in a trace 
paradigm. In vitro studies on hippocampal slices showed that 10-month-old APPLd2 
mice also presented deficits in paired-pulse facilitation and long-term 
potentiation, but presented a normal synaptic activation of CA1 pyramidal cells 
by the stimulation of Schaffer collaterals. It is proposed that definite 
functional changes may appear well in advance of noticeable structural 
alterations in this animal model of Alzheimer's disease, and that specific 
learning tasks could have a relevant diagnostic value.