Reelin protects against amyloid β toxicity in vivo
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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: SCI SIGNAL, Vol. 8, No. 384, 07.07.2015, p. ra67.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Reelin protects against amyloid β toxicity in vivo
AU - Lane-Donovan, Courtney
AU - Philips, Gary T
AU - Wasser, Catherine R
AU - Durakoglugil, Murat S
AU - Masiulis, Irene
AU - Upadhaya, Ajeet
AU - Pohlkamp, Theresa
AU - Coskun, Cagil
AU - Kotti, Tiina
AU - Steller, Laura
AU - Hammer, Robert E
AU - Frotscher, Michael
AU - Bock, Hans H
AU - Herz, Joachim
N1 - Copyright © 2015, American Association for the Advancement of Science.
PY - 2015/7/7
Y1 - 2015/7/7
N2 - 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.
AB - 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.
U2 - 10.1126/scisignal.aaa6674
DO - 10.1126/scisignal.aaa6674
M3 - SCORING: Journal article
C2 - 26152694
VL - 8
SP - ra67
JO - SCI SIGNAL
JF - SCI SIGNAL
SN - 1945-0877
IS - 384
ER -