title: Polymeric complements to the Alzheimer's disease biomarker β-amyloid isoforms Aβ1-40 and Aβ1-42 for blood serum analysis under denaturing conditions.
abstract: Treatment of Alzheimer's disease (AD) is plagued by a lack of practical and reliable methods allowing early diagnosis of the disease. We here demonstrate that robust receptors prepared by molecular imprinting successfully address current limitations of biologically derived receptors in displaying affinity for hydrophobic peptide biomarkers for AD under denaturing conditions. C-terminal epitope-imprinted polymers showing enhanced binding affinity for Aβ1-42 were first identified from a 96-polymer combinatorial library. This information was then used to synthesize molecularly imprinted polymers for both of the β-amyloid (Aβ) isoforms and a corresponding nonimprinted polymer. A solid-phase extraction method was developed to be compatible with sample loading under conditions of complete protein denaturation. This resulted in a method capable of quantitatively and selectively enriching a shorter C-terminal peptide corresponding to the sequences Aβ33-40 and Aβ33-42 as well as the full-length sequence Aβ1-40 and Aβ1-42 from a 4 M guanidinum chloride solution. Application of the method to serum allowed selective, high-recovery extraction of both biomarkers at spiking levels marginally higher than clinically relevant concentrations found in cerebrospinal fluid.
authors.affiliation: INFU, Faculty of Chemistry, Technical University of Dortmund, Otto-Hahn Strasse 6, D-44221 Dortmund, Germany.
authors.forename: Javier L
authors.initials: JL
authors.lastname: Urraca
authors.forename: Carla S A
authors.initials: CS
authors.lastname: Aureliano
authors.forename: Eric
authors.initials: E
authors.lastname: Schillinger
authors.forename: Hermann
authors.initials: H
authors.lastname: Esselmann
authors.forename: Jens
authors.initials: J
authors.lastname: Wiltfang
authors.forename: Börje
authors.initials: B
authors.lastname: Sellergren
mesh_terms: D000544:Alzheimer Disease; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000097:blood* / Q000737:chemistry*; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis / Q000379:methods*; D006801:Humans; D054802:Molecular Imprinting; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000097:blood / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis*; D011489:Protein Denaturation
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; D011108:Polymers; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)