Pre-plaque conformational changes in Alzheimer's disease-linked Aβ and APP
Klementieva, O. (Lund University. Department of Experimental Medical Science)
Willén, K. (Lund University. Department of Experimental Medical Science)
Martinsson, Isak (Lund University. Department of Experimental Medical Science)
Israelsson, B. (Lund University. Department of Experimental Medical Science)
Engdahl, A. (Lund University. MAX IV Laboratory)
Cladera i Cerdà, Josep (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Uvdal, P. (Lund University. Department of Chemistry)
Gouras, G. K. (Lund University. Department of Experimental Medical Science)

Data:	2017
Resum:	Reducing levels of the aggregation-prone Aβ peptide that accumulates in the brain with Alzheimer's disease (AD) has been a major target of experimental therapies. An alternative approach may be to stabilize the physiological conformation of Aβ. To date, the physiological state of Aβ in brain remains unclear, since the available methods used to process brain tissue for determination of Aβ aggregate conformation can in themselves alter the structure and/or composition of the aggregates. Here, using synchrotron-based Fourier transform infrared micro-spectroscopy, non-denaturing gel electrophoresis and conformational specific antibodies we show that the physiological conformations of Aβ and amyloid precursor protein (APP) in brain of transgenic mouse models of AD are altered before formation of amyloid plaques. Furthermore, focal Aβ aggregates in brain that precede amyloid plaque formation localize to synaptic terminals. These changes in the states of Aβ and APP that occur prior to plaque formation may provide novel targets for AD therapy.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Nature communications, Vol. 8 (March 2017) , art. 14726, ISSN 2041-1723

DOI: 10.1038/ncomms14726
PMID: 28287086

9 p, 2.4 MB

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