Development of a quantitative and conformation-sensitive ATR-FTIR biosensor for Alzheimer's disease: The effect of deuteration on the detection of the A beta peptide

Alzheimer's disease (AD) is the most common form of dementia worldwide and represents a glowing socio-economical issue. To date, no reliable diagnosis can be obtained at an early-stage of the disease, though it is now recognized that the aggregation of the amyloid beta (A beta) peptide is responsible or the onset of the disease. Recent studies have shown that soluble amyloid oligomers present in the physiological fluids were the most neurotoxic species and correlated hest with the first signs of cognitive decline, which makes them good biomarkers in the development of a diagnostic tool. We describe here a new type of biosensor, based on attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, that would be able to specifically detect and quantify the presence of the different forms of the A beta peptide in solution. The principle of the detection relies on the recognition of the peptides by specific antibodies that were previously grafted on the surface of an ATR element, consisting of a functionalized germanium crystal. We show that the BIA-ATR technology is able to detect the presence of A beta if incubated in deuterated water and that this step is crucial in the development of our conformation-sensitive biosensor for AD.