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

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Author

  • Davide Tampellini
  • Nawreen Rahman
  • Michael Linell
  • Estibaliz Capetillo-Zarate
  • Gunnar Gouras

Summary, in English

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.

Publishing year

2011

Language

English

Pages

15384-15390

Publication/Series

The Journal of Neuroscience : the official journal of the Society for Neuroscience

Volume

31

Issue

43

Document type

Journal article

Publisher

Society for Neuroscience

Topic

  • Neurosciences

Status

Published

Research group

  • Experimental Dementia Research

ISBN/ISSN/Other

  • ISSN: 1529-2401