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

41 Citations (Scopus)

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

Fingerprint

Amyloid
Apolipoprotein E4
Toxicity
Data storage equipment
Low Density Lipoprotein Receptor-Related Protein-1
Neuronal Plasticity
Learning Disorders
Memory Disorders
Apolipoproteins E
Oligomers
Neurodegenerative Diseases
Neurons
Plasticity
Dementia
Recycling
Brain
Glycoproteins
Alzheimer Disease
Alleles
Learning

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Lane-Donovan, C., Philips, G. T., Wasser, C. R., Durakoglugil, M. S., Masiulis, I., Upadhaya, A., ... Herz, J. (2015). Reelin protects against amyloid β toxicity in vivo. Science Signaling, 8(384), [ra67]. https://doi.org/10.1126/scisignal.aaa6674

Reelin protects against amyloid β toxicity in vivo. / Lane-Donovan, Courtney; Philips, Gary T.; Wasser, Catherine R.; Durakoglugil, Murat S; Masiulis, Irene; Upadhaya, Ajeet; Pohlkamp, Theresa; Coskun, Cagil; Kotti, Tiina; Steller, Laura; Hammer, Robert E; Frotscher, Michael; Bock, Hans H.; Herz, Joachim.

In: Science Signaling, Vol. 8, No. 384, ra67, 07.07.2015.

Research output: Contribution to journalArticle

Lane-Donovan, C, Philips, GT, Wasser, CR, Durakoglugil, MS, Masiulis, I, Upadhaya, A, Pohlkamp, T, Coskun, C, Kotti, T, Steller, L, Hammer, RE, Frotscher, M, Bock, HH & Herz, J 2015, 'Reelin protects against amyloid β toxicity in vivo', Science Signaling, vol. 8, no. 384, ra67. https://doi.org/10.1126/scisignal.aaa6674
Lane-Donovan C, Philips GT, Wasser CR, Durakoglugil MS, Masiulis I, Upadhaya A et al. Reelin protects against amyloid β toxicity in vivo. Science Signaling. 2015 Jul 7;8(384). ra67. https://doi.org/10.1126/scisignal.aaa6674
Lane-Donovan, Courtney ; Philips, Gary T. ; Wasser, Catherine R. ; Durakoglugil, Murat S ; Masiulis, Irene ; Upadhaya, Ajeet ; Pohlkamp, Theresa ; Coskun, Cagil ; Kotti, Tiina ; Steller, Laura ; Hammer, Robert E ; Frotscher, Michael ; Bock, Hans H. ; Herz, Joachim. / Reelin protects against amyloid β toxicity in vivo. In: Science Signaling. 2015 ; Vol. 8, No. 384.
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