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@ARTICLE{vanGroen:840658,
author = {van Groen, Thomas and Schemmert, Sarah and Brener,
Oleksandr and Gremer, Lothar and Ziehm, Tamar and Tusche,
Markus and Nagel-Steger, Luitgard and Kadish, Inga and
Schartmann, Elena and Elfgen, Anne and Jürgens, Dagmar and
Willuweit, Antje and Kutzsche, Janine and Willbold, Dieter},
title = {{T}he {A}β oligomer eliminating {D}-enantiomeric peptide
{RD}2 improves cognition without changing plaque pathology},
journal = {Scientific reports},
volume = {7},
number = {1},
issn = {2045-2322},
address = {London},
publisher = {Nature Publishing Group},
reportid = {FZJ-2017-08159},
pages = {16275},
year = {2017},
abstract = {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.},
cin = {ICS-6 / INM-4},
ddc = {000},
cid = {I:(DE-Juel1)ICS-6-20110106 / I:(DE-Juel1)INM-4-20090406},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000416135000074},
pubmed = {pmid:29176708},
doi = {10.1038/s41598-017-16565-1},
url = {https://juser.fz-juelich.de/record/840658},
}