annelies_vandersteen

-Short Biography

After finishing high school in 2003 I visualized the magnetic field under zero gravity. This unique experience was the outcome of a science contest we participated in during physics class a few months earlier, and it was the ultimate reason to choose for a scientific education. At the Vrije Universiteit Brussel I was seduced by the broad aspects of the bio engineering profile, going from chemistry over physics and math to biotechnology. After an internship at The Coca-Cola Company and a master’s thesis on protein aggregation, I obtained a master in bio engineering. As I got passionate about science during my master’s thesis, I decided to stay in the Switch lab as a PhD student. Halfway through, I moved to the NBP group at Utwente to add a new angle of incidence to my research.

-Contact Information -

A. Vandersteen (Msc, ir.)

Nanobiophysics

University of Twente

MIRA Institute for Biotechnology and Technical Medicine

Zuidhorst ZH153

Drienerlolaan 5

7522 NB  Enschede, the Netherlands

PO-box 217

7500AE Enschede, the Netherlands

P +31-(0)53-489-3163

F +31-(0)53-489-1105


a.vandersteen@utwente.nl

-Own Research in NBP-

TOPIC: Effect of the different Abeta peptide lengths on the stability of toxic oligomers

The deposition of the Amyloid-beta peptide (Ab) in the brain is one of the main hallmarks of Alzheimer’s disease. Ab is released from the Amyloid Precursor Protein (APP) by a proteolytic cleavage which result in a range of Ab peptides varying in length. The longer peptides are more hydrophobic, having far-reaching consequences for their aggregation. The main species in the brain are the 40 and 42 amino acid forms, but the brains of AD patients often contain more of the longer peptides. The total amount of Ab peptides present in the brain is not affected upon development of AD. As Ab is necessary for normal neuronal function, research activity into AD therapeutic development is shifted toward modulating g-secretase activity to produce shorter Ab peptides. However, whether such an approach effectively ameliorates the toxic effect of Ab has not been explored yet. My research focuses on the heterogeneity of the Ab pool in an in vitro biophysical and in cellulo context. I show that various lengths of the Ab peptide aggregate with distinct kinetics and notoriously affect synaptotoxic and cytotoxic responses. Furthermore, we show that small amounts of less abundant peptides Ab38 and Ab43 induce aggregation and toxicity of Ab40 while Ab42 aggregation is not affected.

Publications of interest

(Means publications that either describe your work or your own)

1.

Small, D.H., & McLean, C.A. (1999). Alzheimer’s disease and the Amyloid b Protein. Journal of neurochemistry, 73(2):443-447.

2.

Kuperstein, I, et al. (2010). Neurotoxicity of Alzheimer’s disease Ab peptides is induced by small changes in the Ab42 to Ab40 ratio. EMBO J, 29(19):3408-3420.

3.

Zhou, L., et al. (2011). Amyloid precursor protein mutation E682K at the alternative b-secretase cleavage b’-site increases Ab generation. EMBO Mol Med, 3:1-12.