The risk of suffering from Alzheimer's disease (AD) is higher in individuals from AD-affected mothers. The purpose of this investigation was to study whether maternal transmission might produce AD-related alterations in progenies of mice that do not have any genotypic alteration. We used cognitively-intact mothers harbouring in heterozygosity the transgene for overexpressing the Swedish double mutant version of the human amyloid precursor protein (hA(3PPswe). The phenotype of the offspring with or without the transgene resulting from crossing young Tg2576 females with wild-type males were compared with those of the offspring resulting from crossing wild-type females with Tg2576 males. The hAOPPswe-bearing offspring from Tg2576 mothers showed an aggravated AD-like phenotype. Remarkably, cognitive, immunohistochemica I and some biochemical features displayed by Tg2576 heterozygous mice were also found in wild-type animals generated from Tg2576 females. This suggests the existence of a maternal imprinting in the wild-type offspring that confers a greater facility to launch an AD-like neurodegenerative cascade. Such progeny, lacking any mutant amyloid precursor protein, constitutes a novel model to study maternal transmission of AD and, even more important, to discover early risk markers that predispose to the development of AD.