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Impaired β-Amyloid Secretion in Alzheimer's Disease Pathogenesis.

Tampellini, Davide LU ; Rahman, Nawreen; Linell, Michael; Capetillo-Zarate, Estibaliz and Gouras, Gunnar LU (2011) In The Journal of neuroscience 31(43). p.15384-15390
Abstract
A central question in Alzheimer's disease (AD) research is what role β-amyloid peptide (Aβ) plays in synaptic dysfunction. Synaptic activity increases Aβ secretion, potentially inhibiting synapses, but also decreases intraneuronal Aβ, protecting synapses. We now show that levels of secreted Aβ fall with time in culture in neurons of AD-transgenic mice, but not wild-type mice. Moreover, the ability of synaptic activity to elevate secreted Aβ and reduce intraneuronal Aβ becomes impaired in AD-transgenic but not wild-type neurons with time in culture. We demonstrate that synaptic activity promotes an increase in the Aβ-degrading protease neprilysin at the cell surface and a concomitant increase in colocalization with Aβ42. Remarkably,... (More)
A central question in Alzheimer's disease (AD) research is what role β-amyloid peptide (Aβ) plays in synaptic dysfunction. Synaptic activity increases Aβ secretion, potentially inhibiting synapses, but also decreases intraneuronal Aβ, protecting synapses. We now show that levels of secreted Aβ fall with time in culture in neurons of AD-transgenic mice, but not wild-type mice. Moreover, the ability of synaptic activity to elevate secreted Aβ and reduce intraneuronal Aβ becomes impaired in AD-transgenic but not wild-type neurons with time in culture. We demonstrate that synaptic activity promotes an increase in the Aβ-degrading protease neprilysin at the cell surface and a concomitant increase in colocalization with Aβ42. Remarkably, AD-transgenic but not wild-type neurons show reduced levels of neprilysin with time in culture. This impaired ability to secrete Aβ and reduce intraneuronal Aβ has important implications for the pathogenesis and treatment of AD. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
The Journal of neuroscience
volume
31
issue
43
pages
15384 - 15390
publisher
Society for Neuroscience
external identifiers
  • wos:000296446200017
  • pmid:22031884
  • scopus:80054890505
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.2986-11.2011
language
English
LU publication?
yes
id
0b5d6560-3963-4c84-8f40-dc5d5db310b0 (old id 2200116)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22031884?dopt=Abstract
date added to LUP
2011-11-02 13:55:46
date last changed
2017-11-05 04:11:28
@article{0b5d6560-3963-4c84-8f40-dc5d5db310b0,
  abstract     = {A central question in Alzheimer's disease (AD) research is what role β-amyloid peptide (Aβ) plays in synaptic dysfunction. Synaptic activity increases Aβ secretion, potentially inhibiting synapses, but also decreases intraneuronal Aβ, protecting synapses. We now show that levels of secreted Aβ fall with time in culture in neurons of AD-transgenic mice, but not wild-type mice. Moreover, the ability of synaptic activity to elevate secreted Aβ and reduce intraneuronal Aβ becomes impaired in AD-transgenic but not wild-type neurons with time in culture. We demonstrate that synaptic activity promotes an increase in the Aβ-degrading protease neprilysin at the cell surface and a concomitant increase in colocalization with Aβ42. Remarkably, AD-transgenic but not wild-type neurons show reduced levels of neprilysin with time in culture. This impaired ability to secrete Aβ and reduce intraneuronal Aβ has important implications for the pathogenesis and treatment of AD.},
  author       = {Tampellini, Davide and Rahman, Nawreen and Linell, Michael and Capetillo-Zarate, Estibaliz and Gouras, Gunnar},
  issn         = {1529-2401},
  language     = {eng},
  number       = {43},
  pages        = {15384--15390},
  publisher    = {Society for Neuroscience},
  series       = {The Journal of neuroscience},
  title        = {Impaired β-Amyloid Secretion in Alzheimer's Disease Pathogenesis.},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.2986-11.2011},
  volume       = {31},
  year         = {2011},
}