Description: The Aβ oligomer eliminating D-enantiomeric peptide RD2 improves cognition without changing plaque pathology

This title appears in the Scientific Report : 2017

The Aβ oligomer eliminating D-enantiomeric peptide RD2 improves cognition without changing plaque pathology

While amyloid-β protein (Aβ) aggregation into insoluble plaques is one of the pathological hallmarks of Alzheimer’s disease (AD), soluble oligomeric Aβ has been hypothesized to be responsible for synapse damage, neurodegeneration, learning, and memory deficits in AD. Here, we investigate the in vitr...

Personal Name(s):	van Groen, Thomas (Corresponding author)
	Schemmert, Sarah / Brener, Oleksandr / Gremer, Lothar / Ziehm, Tamar / Tusche, Markus / Nagel-Steger, Luitgard / Kadish, Inga / Schartmann, Elena / Elfgen, Anne / Jürgens, Dagmar / Willuweit, Antje / Kutzsche, Janine / Willbold, Dieter (Corresponding author)
Contributing Institute:	Strukturbiochemie; ICS-6 Physik der Medizinischen Bildgebung; INM-4
Published in:	Scientific reports, 7 (2017) 1, S. 16275
Imprint:	London Nature Publishing Group 2017
PubMed ID:	29176708
DOI:	10.1038/s41598-017-16565-1
Document Type:	Journal Article
Research Program:	Physical Basis of Diseases
Link:	OpenAccess OpenAccess
	Publikationsportal JuSER

Please use the identifier: http://hdl.handle.net/2128/17607 in citations.
Please use the identifier: http://dx.doi.org/10.1038/s41598-017-16565-1 in citations.

While amyloid-β protein (Aβ) aggregation into insoluble plaques is one of the pathological hallmarks of Alzheimer’s disease (AD), soluble oligomeric Aβ has been hypothesized to be responsible for synapse damage, neurodegeneration, learning, and memory deficits in AD. Here, we investigate the in vitro and in vivo efficacy of the d-enantiomeric peptide RD2, a rationally designed derivative of the previously described lead compound D3, which has been developed to efficiently eliminate toxic Aβ42 oligomers as a promising treatment strategy for AD. Besides the detailed in vitro characterization of RD2, we also report the results of a treatment study of APP/PS1 mice with RD2. After 28 days of treatment we observed enhancement of cognition and learning behaviour. Analysis on brain plaque load did not reveal significant changes, but a significant reduction of insoluble Aβ42. Our findings demonstrate that RD2 was significantly more efficient in Aβ oligomer elimination in vitro compared to D3. Enhanced cognition without reduction of plaque pathology in parallel suggests that synaptic malfunction due to Aβ oligomers rather than plaque pathology is decisive for disease development and progression. Thus, Aβ oligomer elimination by RD2 treatment may be also beneficial for AD patients.