Abstract
Alzheimer's disease (AD) is the most common form of dementia worldwide and represents a growing 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 β (Aβ) peptide is responsible for 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 best 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 Aβ 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 Aβ if incubated in deuterated water and that this step is crucial in the development of our conformation-sensitive biosensor for AD.
Highlights
Amyloidoses comprise a series of pathologies sharing a common mechanism of aggregation of misfolded proteins after a conformational change
Two typical hallmarks of this neurodegenerative disorder consist in fibrillar deposits or amyloid plaques in the extraneuronal spaces and neurofibrillary tangles inside the neurons [2]. These so-called senile plaques are mainly composed of the 38–43 residues amyloid β peptide (Aβ), which results from the proteolytic cleavage of the Amyloid Precursor Protein (APP)
The experimental setup allowed us to follow the fixation of the Aβ peptides to antibodies covalently bound to the Ge crystal by recording ATR-FTIR spectra at different time points of the experiment [7,8]
Summary
Amyloidoses comprise a series of pathologies sharing a common mechanism of aggregation of misfolded proteins after a conformational change. Alzheimer’s disease (AD) is a widespread brain-specific amyloidosis affecting more than 30 million people worldwide that is only reliably diagnosed postmortem by the observation of histopathological features of the illness during brain autopsy. Two typical hallmarks of this neurodegenerative disorder consist in fibrillar deposits or amyloid plaques in the extraneuronal spaces and neurofibrillary tangles inside the neurons [2]. These so-called senile plaques are mainly composed of the 38–43 residues amyloid β peptide (Aβ), which results from the proteolytic cleavage of the Amyloid Precursor Protein (APP). E. Kleiren et al / Quantitative and conformation-sensitive ATR-FTIR biosensor for Alzheimer’s disease
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