Project: Effect of early and adult-life stress on the brain epigenome: relevance for the occurrence of Alzheimer’s Disease and Diabetes-related dementia

Acronym EpiAD (Reference Number: PATHWAYS-200-221)
Project Topic Recent human epidemiological and animal experimentation studies have revealed that negative conditions occurring prenatally influence the appearance of metabolic and cardiovascular diseases, some of which are in turn risk factors for Alzheimer’s disease (AD). The aim of this proposal is 1) to determine to which extent prenatal stress (PNS) precipitates AD- and Type 2 Diabetes Mellitus (T2DM)-associated dementia, 2) alone or in combination with a second, adult-life stressor, and 3) whether the early and adult-life stressors lead to changes in the epigenetic regulation of gene expression, which in turn causally contribute to pathology. To tackle these aspects, we will first assess the consequences of PNS on brain development using in utero electroporation and cell type-specific investigations. Second, we will examine the late-life consequences on brain organization and function by non-invasive imaging, behavioral, biochemical, electrophysiological, and epigenetic/transcriptional assays. Comparing these results to those obtained during neurodevelopment will reveal if the late events are part of a developmental, pathological “epigenetic memory”. Thirdly, we will carry out network analysis for identified genes and pathways, followed by gain and loss-of-function via genetic or pharmacological modifiers for proof-ofconcept and interventional strategies. Together these studies will help to determine whether PNS can act as a predisposing factor for the occurrence of AD- and/or T2DM-related cognitive decline, and if so, in the long run to better evaluate people at risk for developing these age-related dementias.
Network JPco-fuND

Project partner

Number Name Role Country
1 Ecole Polytechnique Federale Lausanne Coordinator Switzerland
2 Universitätsklinikum Hamburg-Eppendorf Partner Germany
3 Hospital Universitario La Paz (UAM) Partner Spain
4 Polish Academy of Sciences-Cracow Partner Poland