Pre-plaque conformational changes in Alzheimer’s disease-linked Aβ and APP

O. Klementieva (), K. Willén, I. Martinsson, B. Israelsson, A. Engdahl, J. Cladera, P. Uvdal and G. K. Gouras ()
Additional contact information
O. Klementieva: Experimental Dementia Research Unit, Lund University
K. Willén: Experimental Dementia Research Unit, Lund University
I. Martinsson: Experimental Dementia Research Unit, Lund University
B. Israelsson: Experimental Dementia Research Unit, Lund University
A. Engdahl: MAX IV Laboratory, Lund University
J. Cladera: Universitat Autònoma de Barcelona
P. Uvdal: MAX IV Laboratory, Lund University
G. K. Gouras: Experimental Dementia Research Unit, Lund University

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: Abstract 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.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms14726 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14726

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms14726

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().