Aging is the most significant risk factor for Alzheimer disease (AD). The pathological hallmark of AD is the accumulation of aggregated amyloid-β (Aβ) forms and insoluble plaques, mainly composed of Aβ, in the brain of the patient. Recently, we reported on the selection of d-enantiomeric, Aβ-binding peptides D1 and D3. D1 was selected against aggregated Aβ species to address diagnosis by in vivo imaging of amyloid plaques, whereas D3 was selected using low-molecular-weight Aβ species, therefore addressing therapeutical studies. Here, we use a surface plasmon resonance method to confirm that both peptides show the desired binding specificities.
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References
1.
BrookmeyerR, JohnsonE, Ziegler-GrahamK, ArrighiHM. Forecasting the global burden of Alzheimer's disease. Alzheimers & Dementia, 2007; 3:186–191.
WangR, SweeneyD, GandySE, SisodiaSS. The profile of soluble amyloid β protein in cultured cell media. J Biol Chem, 1996; 271:31894–31902.
4.
HaassC, SelkoeDJ. Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol, 2007; 8:101–112.
XiaW, YangT, ShankarG, SmithIM, ShenY, WalshDM, SelkoeDJ. A specific enzyme-linked immunosorbent assay for measuring beta-amyloid protein oligomers in human plasma and brain tissue of patients with Alzheimer disease. Arch Neurol, 2009; 66:190–199.
7.
LaurénJ, GimbelDA, NygaardHB, GilbertJW, StrittmatterSM. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature, 2009; 26;457:1128–1132.
Van RegenmortelMH, MullerS. D-peptides as immunogens and diagnostic reagents. Curr Opin Biotechnol, 1998; 9:377–382.
10.
WiesehanK, BuderK, LinkeRP, PattS, StoldtM, UngerE, SchmittB, BucciE, WillboldD. Selection of d-amino-acid peptides that bind to Alzheimer's disease amyloid peptide abeta1-42 by mirror image phage display. Chembiochem, 2003; 4:748–753.
11.
van GroenT, KadishI, WiesehanK, FunkeSA, WillboldD. In vitro and in vivo staining characteristics of small, fluorescent, Abeta42-binding d-enantiomeric peptides in transgenic AD mouse models. ChemMedChem, 2009; 4:276–282.
12.
WiesehanK, StöhrJ, Nagel-StegerL, van GroenT, ReisnerD, WillboldD. Inhibition of cytotoxicity and amyloid fibril formation by a d-amino acid peptide that specifically binds to Alzheimer's disease amyloid peptide. Protein Eng Des Sel, 2008; 21:241–246.
13.
van GroenT, WiesehanK, FunkeSA, KadishI, Nagel-StegerL, WillboldD. Reduction of Alzheimer's disease amyloid plaque load in transgenic mice by D3, A d-enantiomeric peptide identified by mirror image phage display. ChemMedChem, 2008; 3:1848–1852.
