ATR-FTIR, a new tool to analyze the oligomeric content of Aβ samples in the presence of apolipoprotein E isoforms

Alzheimer's disease (AD) is a neurodegenerative disorder caused by the aggregation of the amyloid-beta peptide (A beta), leading to amyloid plaques deposition in the brain. Although A beta aggregation pathway still remains unclear, recent studies point out the enhanced toxicity of oligomers compared to fibrils. The E4 isoform of apolipoprotein E (ApoE) is the major risk factor in AD as people carrying one epsilon 4 allele have significantly higher chances to develop the disease. Nevertheless, this phenomenon is still poorly understood. Our group has shown that attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) could discriminate between A beta 42 oligomers and fibrils. Indeed, oligomers display anti-parallel beta-sheet spectral components while fibrils are characterized by a parallel beta-sheet organization. Using those spectral features to analyze the oligomeric content of our samples, we studied the influence of ApoE on A beta 42 aggregation. Our experiments demonstrated that ApoE3 increased the amount of A beta 42 oligomers in the sample. We can thus determine the proportion of A beta oligomers in the presence of another compound in the sample. We plan to use ATR-FTIR to assess the effects of the other isoforms of ApoE on A beta aggregation. Moreover, this could be extended to study the influence of other molecules or proteins on A beta aggregation.