Areas of investigation/research focus
Cerebral small vessel disease and amyloid β (Aβ) deposits are common features of the aging brain. They are presumed to act together to accelerate cognitive aging and dementia development. We here focus on the interplay and the possible causal relationship between small vessel wall damage, i.e. blood-brain barrier breakdown, and the accumulation of pathological proteins, such as Ab. Our research thereby focusses on human and experimental data.
We work in the field of human and experimental cerebral small vessel disease (CSVD). Our human research focusses on large cohort-studies of patients suffering from hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA), with a special interest in understanding the meaning of patients displaying both – HA- and CAA-related features. We further study CSVD patients applying ultra-high resolution 7T MRI, lifestyle and cognitive testing as well as advanced biomarker research (together with Prof. Dr. Emrah Düzel & Prof. Dr. Anne Maass, DZNE Magdeburg).
Experimentally, we use the spontaneously hypertensive stroke-prone rat (SHRSP), a valid non-transgenic model of CSVD, to investigate the interplay between HA and CAA. Using the intravital 2-photon microscopy we showed that HA progresses in a temporal and age-dependent manner, starting from small vessel wall damage, proceeding to cerebral blood flow (CBF) reduction, non-occlusive and finally occlusive thrombus formation (figure 1A-E). In addition to an advanced vascular damage / thrombus formation wall-adherent Aβ accumulations in terms of CAA could be detected (Figure 1D-E). Consequently, the formation and development of CAA seems to occur faster in the presence of a (severe) HA.
Together with the group of Prof. Dr. Alexander Dityatev, DZNE Magdeburg, we further focus on the relationship between CSVD, extracellular matrix remodeling and synaptic plasticity in several experimental models of small vessel disease.
We additionally work on the understanding of the genetic background of CSVD (together with Prof. Dr. Michael Sendtner, Institute of Clinical Neurobiology, University of Würzburg), and how this relates to the behavior of the experimental CSVD models (together with Prof. Dr. Axel Becker, Institute for Pharmacology and Toxicology, Otto-von-Guericke University Magdeburg).
Together with Prof. Dr. Ildiko Dunay, Institute of Inflammation and Neurodegeneration, Otto-von-Guericke University Magdeburg, our focus lies on the investigation of blood-brain barrier breakdown, neurovascular unit damage and stroke-related inflammation in CSVD.