In vitro and in vivo staining characteristics of small, fluorescent, Abeta42-binding D-enantiomeric peptides in transgenic AD mouse models.
One of the characteristic pathological hallmarks of Alzheimer's disease (AD) are neuritic plaques that consist of amyloid peptide (Abeta). To improve diagnosis and treatment evaluation, neuroimaging tools that make use of Abeta-binding ligands to visualise amyloid plaques are being developed. We investigate the in vitro and in vivo characteristics of a series of three D-enantiomeric peptides (D1-D3) that were developed to specifically bind amyloid beta1-42 (Abeta42) in the brains of transgenic AD-model mice. We stained brain sections of the mice, injected and infused the mice with these small D-peptides, and examined their staining of Abeta42 in the brain. The experiments demonstrate that the D-peptides label all plaques that contain Abeta42 in the brain. In contrast, diffuse amyloid beta deposits (which do not contain Abeta42) are not stained by any of the D-peptides. The in vivo and in vitro studies demonstrate that the D-peptides label all Abeta42 in the brain, and none of the D-peptides causes inflammation or is taken up by astrocytes or microglia. Furthermore, long-term infusion of the peptides does not cause inflammation. Together, this demonstrates that these D-peptides might be suitable for use as molecular probes to measure Abeta plaque load in the living brain for early diagnosis of Alzheimer's disease, or to monitor Abeta42 plaque load during disease progression or during treatment.
van Groen
Thomas
T
Department of Cell Biology, University of Alabama at Birmingham, 35294, USA. vangroen@uab.edu
Kadish
Inga
I
Wiesehan
Katja
K
Funke
Susanne A
SA
Willbold
Dieter
D
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000737:chemistry*; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D013237:Stereoisomerism
D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D010455:Peptides; C075222:amyloid beta-protein (1-42)