Reelin protects against amyloid β toxicity in vivo

Courtney Lane-Donovan, Gary T. Philips, Catherine R. Wasser, Murat S Durakoglugil, Irene Masiulis, Ajeet Upadhaya, Theresa Pohlkamp, Cagil Coskun, Tiina Kotti, Laura Steller, Robert E Hammer, Michael Frotscher, Hans H. Bock, Joachim Herz

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Alzheimer's disease (AD) is a currently incurable neurodegenerative disorder and is the most common form of dementia in people over the age of 65 years. The predominant genetic risk factor for AD is the ε4 allele encoding apolipoprotein E (ApoE4). The secreted glycoprotein Reelin enhances synaptic plasticity by binding to the multifunctional ApoE receptors apolipoprotein E receptor 2 (Apoer2) and very low density lipoprotein receptor (Vldlr). We have previously shown that the presence of ApoE4 renders neurons unresponsive to Reelin by impairing the recycling of the receptors, thereby decreasing its protective effects against amyloid β (Aβ) oligomer-induced synaptic toxicity in vitro. We showed that when Reelin was knocked out in adult mice, these mice behaved normally without overt learning or memory deficits. However, they were strikingly sensitive to amyloid-induced synaptic suppression and had profound memory and learning disabilities with very low amounts of amyloid deposition. Our findings highlight the physiological importance of Reelin in protecting the brain against Aβ-induced synaptic dysfunction and memory impairment.

Original languageEnglish (US)
Article numberra67
JournalScience signaling
Volume8
Issue number384
DOIs
StatePublished - Jul 7 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Reelin protects against amyloid β toxicity in vivo'. Together they form a unique fingerprint.

  • Cite this

    Lane-Donovan, C., Philips, G. T., Wasser, C. R., Durakoglugil, M. S., Masiulis, I., Upadhaya, A., Pohlkamp, T., Coskun, C., Kotti, T., Steller, L., Hammer, R. E., Frotscher, M., Bock, H. H., & Herz, J. (2015). Reelin protects against amyloid β toxicity in vivo. Science signaling, 8(384), [ra67]. https://doi.org/10.1126/scisignal.aaa6674