title: Amyloid-β-Secondary Structure Distribution in Cerebrospinal Fluid and Blood Measured by an Immuno-Infrared-Sensor: A Biomarker Candidate for Alzheimer's Disease.
abstract: The misfolding of the Amyloid-beta (Aβ) peptide into β-sheet enriched conformations was proposed as an early event in Alzheimer's Disease (AD). Here, the Aβ 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 Aβ peptides extracted from the body fluid. We observed a significant downshift of the amide I band frequency of Aβ peptides in Dementia Alzheimer type (DAT) patients, which indicated an overall shift to β-sheet. The secondary structure distribution of all Aβ peptides provides a better marker for DAT detection than a single Aβ 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.
authors.affiliation: Department of Biophysics, Ruhr-University Bochum , 44780 Bochum, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Nabers
authors.affiliation: Department of Biophysics, Ruhr-University Bochum , 44780 Bochum, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Ollesch
authors.affiliation: Department of Biophysics, Ruhr-University Bochum , 44780 Bochum, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Schartner
authors.affiliation: Department of Biophysics, Ruhr-University Bochum , 44780 Bochum, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Kötting
authors.affiliation: Clinics for Psychiatry and Psychotherapy, LVR-Clinical Center Essen , 45147 Essen, Germany.
authors.forename: Just
authors.initials: J
authors.lastname: Genius
authors.affiliation: Clinics for Psychiatry and Psychotherapy, LVR-Clinical Center Essen , 45147 Essen, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Hafermann
authors.affiliation: Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, University Medical Center , 37099 Göttingen, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Klafki
authors.affiliation: Department of Biophysics, Ruhr-University Bochum , 44780 Bochum, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Gerwert
authors.affiliation: Clinics for Psychiatry and Psychotherapy, LVR-Clinical Center Essen , 45147 Essen, Germany.|Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, University Medical Center , 37099 Göttingen, Germany.|German Center for Neurodegenerative Diseases (DZNE) , 37099 Göttingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Wiltfang
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry*; D015415:Biomarkers / Q000097:blood* / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers