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

Klementieva, O. LU ; Willén, K. LU ; Martinsson, I. LU ; Israelsson, B. LU ; Engdahl, A. LU ; Cladera, J.; Uvdal, P. LU and Gouras, G. K. LU (2017) In Nature Communications 8.
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... (More)

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.

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author
organization
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type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
8
publisher
Nature Publishing Group
external identifiers
  • scopus:85015324796
  • wos:000396231000001
ISSN
2041-1723
DOI
10.1038/ncomms14726
language
English
LU publication?
yes
id
a1e0dc7a-c70e-46ad-a771-d7cf8f86781e
date added to LUP
2017-03-29 12:29:40
date last changed
2017-09-18 11:34:23
@article{a1e0dc7a-c70e-46ad-a771-d7cf8f86781e,
  abstract     = {<p>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.</p>},
  articleno    = {14726},
  author       = {Klementieva, O. and Willén, K. and Martinsson, I. and Israelsson, B. and Engdahl, A. and Cladera, J. and Uvdal, P. and Gouras, G. K.},
  issn         = {2041-1723},
  language     = {eng},
  month        = {03},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Pre-plaque conformational changes in Alzheimer's disease-linked Aβ and APP},
  url          = {http://dx.doi.org/10.1038/ncomms14726},
  volume       = {8},
  year         = {2017},
}