Accordingly, the severity of cognitive deficits in AD correlates more strongly with the levels of soluble forms of Aβ than with insoluble amyloid plaque load [26] and impairment of hippocampal synaptic plasticity is detected before the formation of insoluble Aβ plaques in amyloid-β precursor protein (APP) transgenic mouse models of AD [28]. Here, APP is linked to Alzheimer disease.