Format

Send to

Choose Destination
Nat Commun. 2014 Mar 6;5:3443. doi: 10.1038/ncomms4443.

Reelin delays amyloid-beta fibril formation and rescues cognitive deficits in a model of Alzheimer's disease.

Author information

1
1] Department of Cell Biology, University of Barcelona, Barcelona 08028, Spain [2] Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid 28031, Spain [3] Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain [4] Vall D'Hebrón Institut de Recerca (VHIR), Barcelona 08035, Spain [5].
2
1] Department of Cell Biology, University of Barcelona, Barcelona 08028, Spain [2] Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid 28031, Spain [3] Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain [4].
3
1] Department of Cell Biology, University of Barcelona, Barcelona 08028, Spain [2] Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid 28031, Spain [3] Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain.
4
Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain.
5
1] Department of Cell Biology, University of Barcelona, Barcelona 08028, Spain [2] Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid 28031, Spain [3] Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain [4] CIEN Foundation, Madrid 28031, Spain.
6
Department of Experimental Sciences and Health, University Pompeu Fabra, Barcelona 08003, Spain.
7
1] Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain [2] Department of Organic Chemistry, University of Barcelona, Barcelona 08028, Spain.
8
1] Department of Cell Biology, University of Barcelona, Barcelona 08028, Spain [2] Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid 28031, Spain [3] Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain [4] Vall D'Hebrón Institut de Recerca (VHIR), Barcelona 08035, Spain [5] CIEN Foundation, Madrid 28031, Spain.

Abstract

Reelin is an extracellular matrix protein that is crucial for neural development and adult brain plasticity. While the Reelin signalling cascade has been reported to be associated with Alzheimer's disease (AD), the role of Reelin in this pathology is not understood. Here we use an in vitro approach to show that Reelin interacts with amyloid-β (Aβ42) soluble species, delays Aβ42 fibril formation and is recruited into amyloid fibrils. Furthermore, Reelin protects against both the neuronal death and dendritic spine loss induced by Aβ42 oligomers. In mice carrying the APP(Swe/Ind) mutation (J20 mice), Reelin overexpression delays amyloid plaque formation and rescues the recognition memory deficits. Our results indicate that by interacting with Aβ42 soluble species, delaying Aβ plaque formation, protecting against neuronal death and dendritic spine loss and preventing AD cognitive deficits, the Reelin pathway deserves consideration as a therapeutic target for the treatment of AD pathogenesis.

PMID:
24599114
DOI:
10.1038/ncomms4443
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center