Epsilon Archive for Student Projects

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. The pathogenesis of AD is linked to the oligomerization and aggregation of the amyloid-β peptide (Aβ) into protein plaques in the brain. However, the role of these aggregates in the disease pathology remains largely unknown. An important hypothesis today is that neurotoxic oligomeric Aβ aggregates are responsible for cell death. And there might be interaction of neurotoxic oligomeric Aβ with other proteins in human biological fluids that might be involved in amyloid-β neurotoxicity. The project was aimed in identifying which proteins in human biological fluids interact with neurotoxic oligomeric form of Aβ.

A proteomics approach has been developed in which stable oligomers formed by a modified Aβ peptide (Aβ42cc) have been used to capture protein ligands in human serum and cerebrospinal fluid (CSF). The captured proteins have then been separated by gel electrophoresis and characterized by mass spectrometry. Five proteins in human serum have been identified as Apolipoprotein A-I, Apolipoprotein E, Apolipoprotein A-IV, Vitronectin and Antithrombin III. Six CSF samples have been investigated of which three were from AD patients and three from healthy individuals. Four proteins in different CSF samples have been identified as Apolipoprotein A-I, Apolipoprotein E, Clusterin and Gelsolin. Our results show that there are interactions between Aβ42cc oligomers and other proteins in serum and CSF.