Sabrina Tschickardt

Spenden & Helfen
 
 

Curriculum vitae

Name Sabrina Tschickardt
Place of Birth Mainz, Germany
Dateof Birth January 31, 1984
   
01/2010 - present PhD-student at the University Medical Center of the Johannes Gutenberg-University of Mainz, Institute of Pathobiochemistry in the “Molecular Neurodegeneration” group of Prof. Dr. Claus Pietrzik
01/2009 - 09/2009 Diploma thesis at Boehringer Inghelheim Pharma GmbH & Co.KG, Department CNS, Group CNS Research III, 88397 Biberach an der Riss, Germany, Topic: "Analysis of PDE9 function in neuronal systems" with Dr. Cornelia Dorner-Ciossek (Grade: 1.1*)   
08/2007 - 01/2008 Exchange Student at the Århus University in Denmark
04/2004 - 09/2009 Degree programme: Biology, Johannes Gutenberg-University Mainz, Degree: Diploma (Grade: 1.1*)
04/2003 - 03/2004 Red Cross Pain Center in Mainz, Exercise in nursing service
 

Project description

The blood-brain barrier and Alzheimer’s disease

Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting 26 million people to date and this number will increase to approximately 140 million people until 2050. AD is characterized by neurofibrillary tangles and extracellular deposits of amyloid- (Aβ) peptides. Aβ deposition in the hippocampus results in learning and memory deficits and ultimately neuronal loss, but Aβ has also been found in cerebral blood vessel walls, a symptom referred to as cerebral amyloid angiopathy (CAA). To date, AD is incurable and there have been lots of efforts for its treatment. One of it is to increase Aβ elimination from the brain, for example across the blood-brain barrier (BBB) into the blood stream.
The BBB separates the circulating blood from the central nervous system (CNS) and plays a crucial role in brain homeostasis. Furthermore, it is essential for the supply of the CNS with nutrients, but also in restricting access of many substances from the blood into the brain. The BBB is comprised of pericytes, astrocytes and endothelial cells (ECs). Tight junctions between ECs are an essential part of the BBB because they close the intercellular space between ECs and, thereby limit paracellular flux of hydrophilic molecules across the BBB. To supply the CNS with nutrients, ECs express a large number of specialized transporters and receptors. To date, few transporters and receptors have been identified in Aβ transport across the BBB, but the mechanisms are still unclear.
P-glycoprotein (P-gp), an ATP-driven efflux transporter that limits CNS penetration of drugs, was shown to mediate the transport of Aβ across the BBB in vivo and in vitro. However, some studies failed to show an effect of P-gp in Aβ transport from brain to blood. Thus, further investigation of the distinct role of P-gp in this paradigm might open new approaches for the treatment of AD.
An additional approach for the treatment of AD is the interference with Aβ1-42 production in the brain. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to alter β-secretase activity and to selectively lower Aβ1-42 production, which is thought to play a central role in AD pathogenesis. However, NSAIDs do not cross the BBB at high enough concentrations. Recently, apolipoprotein-modified human serum albumin (HSA) nanoparticles have been shown to carry non-permeable drugs over the BBB. Using NSAIDs coupled to nanoparticles could overcome the poor BBB permeability of NSAIDs alone and, thereby modulate Aβ1-42 production in the brain of AD patients.