Amyloid-β-Secondary Structure Distribution in Cerebrospinal Fluid and Blood Measured by an Immuno-Infrared-Sensor: A Biomarker Candidate for Alzheimer's Disease

The misfolding of the Amyloid-beta (A beta) peptide into beta-sheet enriched conformations was proposed as an early event in Alzheimer's Disease (AD). Here, the A beta peptide secondary structure distribution in cerebrospinal fluid (CSF) and blood plasma of 141 patients was measured with an immuno-infrared-sensor. The sensor detected the amide I band, which reflects the overall secondary structure distribution of all A beta peptides extracted from the body fluid. We observed a significant downshift of the amide I band frequency of A beta peptides in Dementia Alzheimer type (DAT) patients, which indicated an overall shift to beta-sheet. The secondary structure distribution of all A beta peptides provides a better marker for DAT detection than a single A beta misfold or the concentration of a specific oligomer. The discrimination between DAT and disease control patients according to the amide I frequency was in excellent agreement with the clinical diagnosis (accuracy 90% for CSF and 84% for blood). The amide I band maximum above or below the decisive marker frequency appears as a novel spectral biomarker candidate of AD. Additionally, a preliminary proof-of-concept study indicated an amide I band shift below the marker band already in patients with mild cognitive impairment due to AD. The presented immuno-IR-sensor method represents a promising, simple, robust, and label-free diagnostic tool for CSF and blood analysis.