Synchrotron-Based Fourier Transform Infrared Microspectroscopy (μFTIR) Study on the Effect of Alzheimer’s Aβ Amorphous and Fibrillar Aggregates on PC12 Cells

5 years ago

Synchrotron-Based Fourier Transform Infrared Microspectroscopy (μFTIR) Study on the Effect of Alzheimer’s Aβ Amorphous and Fibrillar Aggregates on PC12 Cells

Carlos Falcon, Elena Álvarez-Marimon, Marine Cotte, Josep Cladera, Hiram Castillo-Michel, Núria Benseny-Cases

Amyloid plaques made of aggregated Aβ amyloid peptide are a pathological hallmark in brains affected by Alzheimer’s disease. Moreover, the amyloid peptide may play a major role in the onset and development of the disease in association to other factor such as oxidative stress. Although the molecular nature of the amyloid toxic species is still unknown, there is experimental evidence pointing to their non-fibrillar nature. In the present paper we report the use of FTIR microspectroscopy (µFTIR) for the study of the effect of two different types of Alzheimer’s Aβ(1-40) aggregates (amyloid fibrils and granular non-fibrillar aggregates on PC12 cultured cells. The Principal Component Analysis (PCA) of the infrared spectra has been complemented with a correlation analysis which permits to study different spectroscopic parameters as a function of peptide aggregation. The results show that the treatment of PC12 cells with amorphous aggregates generates a higher degree of oxidation in the vicinity of the amyloid aggregates than the treatment with pre-formed amyloid fibrils. These results, which permits for the first time the in situ co-localization of amyloid aggregates and oxidized macromolecules in cell culture, are in agreement with previous data from our group showing that oxidation was higher in regions surrounding amyloid plaques in human brain samples affected by Alzheimer’s disease.

Publisher URL: http://dx.doi.org/10.1021/acs.analchem.7b04818

DOI: 10.1021/acs.analchem.7b04818