Kerensa Broersen
University of Twente, The Netherlands
Title: An investigation into amyloid beta peptide variation as Alzheimer’s disease progress
Biography
Biography: Kerensa Broersen
Abstract
One of the most prominent hallmarks detected in the brain of patients suffering from Alzheimer’s disease is the deposition of amyloidogenic plaques. These plaques are largely composed of the amyloid-beta peptide. It has been demonstrated that, even though these plaques comprise an important and recurring feature for disease, that precursor forms of these plaques, called ‘oligomers’ or ‘protofibrils’ more potently affect neuronal functioning. The amyloid-beta peptide arises from cleavage of trans-membrane amyloid precursor protein through cleavage by means of a combination of secretase enzymes. As a result of this enzymatic processing, genetic profile and further modifications, the amyloid beta peptide does not exist as a well-defined species but arises in a variety of truncated and modified forms. For example, it has been reported that, within any one individual, a range of amyloid beta peptides exist varying in length from 34 to 49 amino acids and that multiple otherwise modified forms of this peptide are present in a complex mixture. We have shown that small shifts in the composition of the amyloid beta pool can have significant impact on the aggregation reaction, cellular response and cognitive behavior in animal models. The mechanism by which hence formed variants of the amyloid-beta peptide cause disease still remains elusive. In aim to determine how amyloid beta peptide manifests its pathological effects, we use Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy, mass spectrometry and immunohistochemistry to monitor peptide aggregation.