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Apolipoprotein E loss of function: Influence on murine brain markers of physiology and pathology

The canonical role of Apolipoprotein E (ApoE) is related to lipid and cholesterol metabolism, however, additional functions of this protein have not been fully described. Given the association of ApoE with diseases such as Alzheimer’s Disease (AD), it is clear that further characterisation of its ro...

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Autores principales: Buchanan, Heather, Hull, Claire, Cacho Barraza, Maria, Delibegovic, Mirela, Platt, Bettina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9997145/
https://www.ncbi.nlm.nih.gov/pubmed/36908879
http://dx.doi.org/10.1016/j.nbas.2022.100055
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author Buchanan, Heather
Hull, Claire
Cacho Barraza, Maria
Delibegovic, Mirela
Platt, Bettina
author_facet Buchanan, Heather
Hull, Claire
Cacho Barraza, Maria
Delibegovic, Mirela
Platt, Bettina
author_sort Buchanan, Heather
collection PubMed
description The canonical role of Apolipoprotein E (ApoE) is related to lipid and cholesterol metabolism, however, additional functions of this protein have not been fully described. Given the association of ApoE with diseases such as Alzheimer’s Disease (AD), it is clear that further characterisation of its roles, especially within the brain, is needed. Therefore, using protein and gene expression analyses of neonatal and 6-month old brain tissues from an ApoE knockout mouse model, we examined ApoE’s contribution to several CNS pathways, with an emphasis on those linked to AD. Early neonatal changes associated with ApoE−/− were observed, with decreased soluble phosphorylated tau (p-tau, –40 %), increased synaptophysin (+36 %) and microglial Iba1 protein levels (+25 %) vs controls. Progression of the phenotype was evident upon analysis of 6-month-old tissue, where decreased p-tau was also confirmed in the insoluble fraction, alongside reduced synaptic and increased amyloid precursor protein (APP) protein levels. An age comparison further underlined deviations from WT animals and thus the impact of ApoE loss on neuronal maturation. Taken together, our data implicate ApoE modulation of multiple CNS roles. Loss of function is associated with alterations from birth, and include synaptic deficits, neuroinflammation, and changes to key AD pathologies, amyloid-β and tau.
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spelling pubmed-99971452023-03-09 Apolipoprotein E loss of function: Influence on murine brain markers of physiology and pathology Buchanan, Heather Hull, Claire Cacho Barraza, Maria Delibegovic, Mirela Platt, Bettina Aging Brain Article The canonical role of Apolipoprotein E (ApoE) is related to lipid and cholesterol metabolism, however, additional functions of this protein have not been fully described. Given the association of ApoE with diseases such as Alzheimer’s Disease (AD), it is clear that further characterisation of its roles, especially within the brain, is needed. Therefore, using protein and gene expression analyses of neonatal and 6-month old brain tissues from an ApoE knockout mouse model, we examined ApoE’s contribution to several CNS pathways, with an emphasis on those linked to AD. Early neonatal changes associated with ApoE−/− were observed, with decreased soluble phosphorylated tau (p-tau, –40 %), increased synaptophysin (+36 %) and microglial Iba1 protein levels (+25 %) vs controls. Progression of the phenotype was evident upon analysis of 6-month-old tissue, where decreased p-tau was also confirmed in the insoluble fraction, alongside reduced synaptic and increased amyloid precursor protein (APP) protein levels. An age comparison further underlined deviations from WT animals and thus the impact of ApoE loss on neuronal maturation. Taken together, our data implicate ApoE modulation of multiple CNS roles. Loss of function is associated with alterations from birth, and include synaptic deficits, neuroinflammation, and changes to key AD pathologies, amyloid-β and tau. Elsevier 2022-11-01 /pmc/articles/PMC9997145/ /pubmed/36908879 http://dx.doi.org/10.1016/j.nbas.2022.100055 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Buchanan, Heather
Hull, Claire
Cacho Barraza, Maria
Delibegovic, Mirela
Platt, Bettina
Apolipoprotein E loss of function: Influence on murine brain markers of physiology and pathology
title Apolipoprotein E loss of function: Influence on murine brain markers of physiology and pathology
title_full Apolipoprotein E loss of function: Influence on murine brain markers of physiology and pathology
title_fullStr Apolipoprotein E loss of function: Influence on murine brain markers of physiology and pathology
title_full_unstemmed Apolipoprotein E loss of function: Influence on murine brain markers of physiology and pathology
title_short Apolipoprotein E loss of function: Influence on murine brain markers of physiology and pathology
title_sort apolipoprotein e loss of function: influence on murine brain markers of physiology and pathology
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9997145/
https://www.ncbi.nlm.nih.gov/pubmed/36908879
http://dx.doi.org/10.1016/j.nbas.2022.100055
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