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ApoE4 delays dendritic spine formation during neuron development and accelerates loss of mature spines in vitro

The ε4 allele of the gene that encodes apolipoprotein E (APOE4) is the greatest genetic risk factor for Alzheimer's disease (AD), while APOE2 reduces AD risk, compared to APOE3. The mechanism(s) underlying the effects of APOE on AD pathology remains unclear. In vivo, dendritic spine density is...

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Autores principales: Nwabuisi-Heath, Evelyn, Rebeck, G. William, LaDu, Mary Jo, Yu, Chunjiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Neurochemistry 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891498/
https://www.ncbi.nlm.nih.gov/pubmed/24328732
http://dx.doi.org/10.1042/AN20130043
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author Nwabuisi-Heath, Evelyn
Rebeck, G. William
LaDu, Mary Jo
Yu, Chunjiang
author_facet Nwabuisi-Heath, Evelyn
Rebeck, G. William
LaDu, Mary Jo
Yu, Chunjiang
author_sort Nwabuisi-Heath, Evelyn
collection PubMed
description The ε4 allele of the gene that encodes apolipoprotein E (APOE4) is the greatest genetic risk factor for Alzheimer's disease (AD), while APOE2 reduces AD risk, compared to APOE3. The mechanism(s) underlying the effects of APOE on AD pathology remains unclear. In vivo, dendritic spine density is lower in APOE4-targeted replacement (APOE-TR) mice compared with APOE2- and APOE3-TR mice. To investigate whether this apoE4-induced decrease in spine density results from alterations in the formation or the loss of dendritic spines, the effects of neuron age and apoE isoform on the total number and subclasses of spines were examined in long-term wild-type neurons co-cultured with glia from APOE2-, APOE3- and APOE4-TR mice. Dendritic spine density and maturation were evaluated by immunocytochemistry via the presence of drebrin (an actin-binding protein) with GluN1 (NMDA receptor subunit) and GluA2 (AMPA receptor subunit) clusters. ApoE isoform effects were analyzed via a method previously established that identifies phases of spine formation (day-in-vitro, DIV10–18), maintenance (DIV18–21) and loss (DIV21–26). In the formation phase, apoE4 delayed total spine formation. During the maintenance phase, the density of GluN1+GluA2 spines did not change with apoE2, while the density of these spines decreased with apoE4 compared to apoE3, primarily due to the loss of GluA2 in spines. During the loss phase, total spine density was lower in neurons with apoE4 compared to apoE3. Thus, apoE4 delays total spine formation and may induce early synaptic dysfunction via impaired regulation of GluA2 in spines.
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spelling pubmed-38914982014-01-27 ApoE4 delays dendritic spine formation during neuron development and accelerates loss of mature spines in vitro Nwabuisi-Heath, Evelyn Rebeck, G. William LaDu, Mary Jo Yu, Chunjiang ASN Neuro Research Article The ε4 allele of the gene that encodes apolipoprotein E (APOE4) is the greatest genetic risk factor for Alzheimer's disease (AD), while APOE2 reduces AD risk, compared to APOE3. The mechanism(s) underlying the effects of APOE on AD pathology remains unclear. In vivo, dendritic spine density is lower in APOE4-targeted replacement (APOE-TR) mice compared with APOE2- and APOE3-TR mice. To investigate whether this apoE4-induced decrease in spine density results from alterations in the formation or the loss of dendritic spines, the effects of neuron age and apoE isoform on the total number and subclasses of spines were examined in long-term wild-type neurons co-cultured with glia from APOE2-, APOE3- and APOE4-TR mice. Dendritic spine density and maturation were evaluated by immunocytochemistry via the presence of drebrin (an actin-binding protein) with GluN1 (NMDA receptor subunit) and GluA2 (AMPA receptor subunit) clusters. ApoE isoform effects were analyzed via a method previously established that identifies phases of spine formation (day-in-vitro, DIV10–18), maintenance (DIV18–21) and loss (DIV21–26). In the formation phase, apoE4 delayed total spine formation. During the maintenance phase, the density of GluN1+GluA2 spines did not change with apoE2, while the density of these spines decreased with apoE4 compared to apoE3, primarily due to the loss of GluA2 in spines. During the loss phase, total spine density was lower in neurons with apoE4 compared to apoE3. Thus, apoE4 delays total spine formation and may induce early synaptic dysfunction via impaired regulation of GluA2 in spines. American Society for Neurochemistry 2014-01-13 /pmc/articles/PMC3891498/ /pubmed/24328732 http://dx.doi.org/10.1042/AN20130043 Text en © 2014 The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Licence (CC-BY)(http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC-BY) (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Nwabuisi-Heath, Evelyn
Rebeck, G. William
LaDu, Mary Jo
Yu, Chunjiang
ApoE4 delays dendritic spine formation during neuron development and accelerates loss of mature spines in vitro
title ApoE4 delays dendritic spine formation during neuron development and accelerates loss of mature spines in vitro
title_full ApoE4 delays dendritic spine formation during neuron development and accelerates loss of mature spines in vitro
title_fullStr ApoE4 delays dendritic spine formation during neuron development and accelerates loss of mature spines in vitro
title_full_unstemmed ApoE4 delays dendritic spine formation during neuron development and accelerates loss of mature spines in vitro
title_short ApoE4 delays dendritic spine formation during neuron development and accelerates loss of mature spines in vitro
title_sort apoe4 delays dendritic spine formation during neuron development and accelerates loss of mature spines in vitro
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891498/
https://www.ncbi.nlm.nih.gov/pubmed/24328732
http://dx.doi.org/10.1042/AN20130043
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