Grant awarded for research on Alzheimer and epigenetics for Carlos Fitzsimons
Dr Carlos Fitzsimons of the Swammerdam Institute for Life Sciences was awarded a €100,000 grant by the International Foundation for Alzheimer Research (ISAO) for his 2-year project entitled: Epigenetic programming of hippocampal neurogenesis by stress in sporadic Alzheimer’s disease models.
The risk of Alzheimer's disease (AD) is partly determined by age, genetic (family) influences and environmental factors. A key factor in this process is played by changes in the folding and "accessibility" of DNA, the so-called 'epigenetic' processes. Stress is an important environmental factor which can not only increase the risk of AD, but also induce epigenetic changes such as DNA methylation. DNA methylation changes brain cells, and possibly also the birth of new neurons in the adult brain. This process of so-called "neurogenesis" plays a role in learning and memory, and is also affected by stress, epigenetics and the presence of Alzheimer's proteins.
Most current animal models of Alzheimer’s disease (AD) are based on the expression of mutated genes associated with the familiar form of AD. These models have played a major role in identifying pathological mechanisms linked to and in evaluating novel therapies. However, familial AD affects only a minority of AD patients. Moreover, in these models pathology starts early in life and is driven fundamentally by the expression of the mutated gene, making them especially unsuitable for the study of the effect of environmental factors, such as stress, on AD progression.
Fitzsimons plans on using sensitive, modern techniques to identify how external (environmental) factors such as stress, causes changes in epigenetics, and what those changes are. He will also determine how these changes may affect the new nerve cells, their synaptic connections and their function in cultures and animal dementia models.