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

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-? (A?42) soluble species, delays A?42 fibril formation and is recruited into amyloid fibrils. Furthermore, Reelin protects against both the neuronal death and dendritic spine loss induced by A?42 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 A?42 soluble species, delaying A? 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.
Mesh Terms:
Alzheimer Disease, Amyloid, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Behavior, Animal, Blotting, Western, Brain, Cell Adhesion Molecules, Neuronal, Cells, Cultured, Cognition Disorders, Dendritic Spines, Disease Models, Animal, Extracellular Matrix Proteins, HEK293 Cells, Humans, Male, Mice, Mice, Transgenic, Microscopy, Electron, Transmission, Nerve Tissue Proteins, Peptide Fragments, Plaque, Amyloid, Protein Binding, Serine Endopeptidases
Nat Commun
Date: Mar. 06, 2014
Download Curated Data For This Publication
227197
Switch View:
  • Interactions 3