Understanding brain development and decline is of utmost importance in an aging society. MRI Biophysics Research Group aims to uncover crucial mechanisms of human brain aging, by identifying the contribution of iron accumulation, a major determinant of brain development and brain decline. We are developing new specific and sensitive markers for the cellular distribution and the chemical form of iron by integration of cutting-edge MRI with advanced histology and biophysical models. These newly developed markers will be applied in vivo, to gain important new insight into human brain development, plasticity and degeneration. We combine the recent improvement of advanced high-field MRI, latest progress in the understanding of brain iron biochemistry and biophysical modeling to achieve novel MRI brain iron markers with cellular sensitivity. Our goal is to contribute to a mechanistic understanding of the brain iron metabolism and its role in brain development to enable new diagnostics and therapies targeting iron induced neurodegeneration in the future.
Iron in the human brain
Neurodegenerative diseases cause annual treatment costs of more than 100 billion Euros in Europe alone. Due to increasing life expectancies, the number of cases constantly increases, causing not only growing socioeconomic costs but also tremendous suffering. Understanding, predicting and identifying processes contributing to brain decline is therefore a research topic of paramount importance.
Iron plays a central role in brain development and brain aging. Transmission of neuronal signals, ongoing optimization, repair and maintenance of brain structures demand substantial energy and require iron as co-factor for energy supply, myelination and neurotransmitter synthesis. However, iron turns toxic and harmful when present in certain chemical forms and at high concentrations. While high iron uptake is associated with improved cognitive performance in the young, it becomes detrimental with increasing age. After the age of 40, increased iron accumulation leads to faster brain decline, diminished cognitive abilities and increased risk of neurodegenerative diseases. The recent discovery of ferroptosis, iron-dependent programmed cell death, together with advances in the molecular biology of brain iron uncovered the cellular mechanisms of neurodegeneration in animal models. Understanding these mechanisms and following iron trajectories in humans both on the cellular and the whole brain level is key to an in-depth understanding of human brain aging.