Unraveling the link between major depression and Alzheimer's disease: The effects of prenatal stress in the APPswe/PS1dE9 mouse model of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is the most common form of dementia in the elderly. In 2006 the World Health Organization estimated that about 18 million people worldwide suffer from AD and this number is still increasing. Risk factors for AD, such as age, gender and genes, e.g. APP and PS1, are already under investigation for several decades. A disorder that has received growing attention as a risk factor for AD is major depression (MD). Several studies in humans have indicated that a history of MD increases the risk of developing AD, while animal studies show that a depressive-like phenotype increases neuropathology in AD mouse models. Using the APPswe/PS1dE9 mouse model of AD and prenatal stress (PS), a model for MD, the mechanisms underlying the link between MD and AD were investigated in the present study. We hypothesized that exposing APPswe/PS1dE9 mice to PS would increase AD-related neuropathology in the hippocampus, which could possibly explain the observed behavioral alterations.