Reelin protects against amyloid β toxicity in vivo

Topic: Amyloid, tau and blood-test diagnosis

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.

Key findings

• 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.
• Our findings highlight the physiological importance of Reelin in protecting the brain against Aβ-induced synaptic dysfunction and memory impairment.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1126/scisignal.aaa6674
• PubMed: 26152694
• Original source →

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@article{lanedonovan2015-26152694,
  author  = {Lane-Donovan, C. and Philips, G. T. and Wasser, C. R. and Durakoglugil, M. S. and Masiulis, I. and Upadhaya, A. and Pohlkamp, T. and Coskun, C. and others},
  title   = {{Reelin protects against amyloid β toxicity in vivo}},
  journal = {Science signaling},
  year    = {2015},
  doi     = {10.1126/scisignal.aaa6674},
  pmid    = {26152694},
  url     = {https://doi.org/10.1126/scisignal.aaa6674}
}

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