Description: Aβ Oligomer Elimination Restores Cognition in Transgenic Alzheimer’s Mice with Full-blown Pathology

This title appears in the Scientific Report : 2019

Aβ Oligomer Elimination Restores Cognition in Transgenic Alzheimer’s Mice with Full-blown Pathology

Oligomers of the amyloid-β (Aβ) protein are suspected to be responsible for the development and progression of Alzheimer’s disease. Thus, the development of compounds that are able to eliminate already formed toxic Aβ oligomers is very desirable. Here, we describe the in vivo efficacy of the compoun...

Personal Name(s):	Schemmert, Sarah
	Schartmann, Elena / Zafiu, Christian / Kass, Bettina / Hartwig, Sonja / Lehr, Stefan / Bannach, Oliver / Langen, Karl-Josef / Shah, Nadim Joni / Kutzsche, Janine / Willuweit, Antje (Corresponding author) / Willbold, Dieter (Corresponding author)
Contributing Institute:	JARA-BRAIN; JARA-BRAIN Jara-Institut Quantum Information; INM-11 Physik der Medizinischen Bildgebung; INM-4 Strukturbiochemie; ICS-6
Published in:	Molecular neurobiology, 56 (2019) 3, S. 2211-2223
Imprint:	Totowa, NJ Humana Press 2019
PubMed ID:	30003517
DOI:	10.1007/s12035-018-1209-3
Document Type:	Journal Article
Research Program:	Physical Basis of Diseases
Link:	Get full text Get full text OpenAccess OpenAccess
	Publikationsportal JuSER

Please use the identifier: http://hdl.handle.net/2128/21947 in citations.
Please use the identifier: http://dx.doi.org/10.1007/s12035-018-1209-3 in citations.

Oligomers of the amyloid-β (Aβ) protein are suspected to be responsible for the development and progression of Alzheimer’s disease. Thus, the development of compounds that are able to eliminate already formed toxic Aβ oligomers is very desirable. Here, we describe the in vivo efficacy of the compound RD2, which was developed to directly and specifically eliminate toxic Aβ oligomers. In a truly therapeutic, rather than a preventive study, oral treatment with RD2 was able to reverse cognitive deficits and significantly reduce Aβ pathology in old-aged transgenic Alzheimer’s Disease mice with full-blown pathology and behavioral deficits. For the first time, we demonstrate the in vivo target engagement of RD2 by showing a significant reduction of Aβ oligomers in the brains of RD2-treated mice compared to placebo-treated mice. The correlation of Aβ elimination in vivo and the reversal of cognitive deficits in old-aged transgenic mice support the hypothesis that Aβ oligomers are relevant not only for disease development and progression, but also offer a promising target for the causal treatment of Alzheimer’s disease.