Abstract
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 (hAβPPswe). 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 hAβPPswe-bearing offspring from Tg2576 mothers showed an aggravated AD-like phenotype. Remarkably, cognitive, immunohistochemical 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.
Highlights
Two different types of Alzheimer’s disease (AD), which is the most common cause of dementia, are identified on the basis of pathologic, genetic and molecular evidence
We evaluated the spatial memory of the animals by the Morris Water Maze test (MWM)
The test was performed at an age of 8 months, when it has been already demonstrated that the Tg2576 mice do not yet display deficits in spatial memory
Summary
Two different types of Alzheimer’s disease (AD), which is the most common cause of dementia, are identified on the basis of pathologic, genetic and molecular evidence. The early-onset Alzheimer’s disease (EOAD) is due to mutations of human amyloid-β precursor protein (hAβPP) or presenilin genes. Late-onset Alzheimer’s disease (LOAD), the most common form of the disease, is not linked to specific gene alterations and its aetiology is caused by a complex interaction between genetic and life-style factors. The second most important risk factor for LOAD is having a parent with the disease[1,2]. The best studied EOAD -associated mutation is the Swedish double mutation in the hAβPP gene (hAβPPswe)[18]. This mutation has been instrumental to develop the Tg2576 transgenic mouse model, which overexpresses hAβPPswe. The generated animal models, WT and heterozygous Tg2576 animals with maternal imprinting (WTM and Tg2576M), show promise to understand AD maternal transmission and to discover early risk markers that predispose to develop AD
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