HomeAbout the InstituteResearch UnitsPeopleLinksPh.D ProgramEnglish Language Idioma EspañolWeb SearchIntranet Access
 
 
Research highlights About the institute
The β-amyloid peptide compromises Reelin signaling in Alzheimer’s disease.

Scientific Reports 6, Article number: 31646

Published 17 August 2016

Inmaculada Cuchillo-Ibañez, Trinidad Mata-Balaguer, Valeria Balmaceda, Juan José Arranz, Johannes Nimpf & Javier Sáez-Valero

Reelin is a signaling protein that plays a crucial role in synaptic function, which expression is influenced by β-amyloid (Aβ). We show that Reelin and Aβ oligomers co-immunoprecipitated in human brain extracts and were present in the same size-exclusion chromatography fractions. Aβ treatment of cells led to increase expression of Reelin, but secreted Reelin results trapped together with Aβ aggregates. In frontal cortex extracts an increase in Reelin mRNA, and in soluble and insoluble (guanidine-extractable) Reelin protein, was associated with late Braak stages of Alzheimer's disease (AD), while expression of its receptor, ApoER2, did not change. However, Reelin-dependent induction of Dab1 phosphorylation appeared reduced in AD. In cells, Aβ reduced the capacity of Reelin to induce internalization of biotinylated ApoER2 and ApoER2 processing. Soluble proteolytic fragments of ApoER2 generated after Reelin binding can be detected in cerebrospinal fluid (CSF). Quantification of these soluble fragments in CSF could be a tool to evaluate the efficiency of Reelin signaling in the brain. These CSF-ApoER2 fragments correlated with Reelin levels only in control subjects, not in AD, where these fragments diminished. We conclude that while Reelin expression is enhanced in the Alzheimer's brain, the interaction of Reelin with Aβ hinders its biological activity.

Research Highlights Archive

CSIC-UMH
 
 
Consejo Superior de Investigaciones Científicas
Universidad Miguel Hernández

Campus de San Juan | Sant Joan d’Alacant
Alicante | España

in@umh.es
direccion.in@umh.es
Tel. + 34 965 23 37 00
Fax + 34 965 91 95 61
© 2004-2016 Instituto de Neurociencias
Alicante | España | Legal Note | Mapa Web
Diseño web Digital Nature