Interactive effect of age and APOE-ε4 allele load on white matter myelin content in cognitively normal middle-aged subjects
The apolipoprotein E gene (APOE) ε4 allele has a strong and manifold impact on cognition and neuroimaging phenotypes in cognitively normal subjects, including alterations in the white matter (WM) microstructure. Such alterations have often been regarded as a reflection of potential thinning of the m...
| Autores: | , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/162049 |
| Acceso en línea: | https://hdl.handle.net/2445/162049 |
| Access Level: | acceso abierto |
| Palabra clave: | Gens Cognició Malalties neurodegeneratives Lípids Mielina Genes Cognition Neurodegenerative Diseases Lipids Myelin sheath |
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Interactive effect of age and APOE-ε4 allele load on white matter myelin content in cognitively normal middle-aged subjectsOperto, GrégoryMolinuevo, José LuisCacciaglia, RaffaeleFalcón, CarlesBrugulat Serrat, AnnaSuárez Calvet, MarcGrau Rivera, OriolBargalló Alabart, NúriaMoran, SebastianEsteller, Manel, 1968-Gispert, Juan DomingoGensCognicióMalalties neurodegenerativesLípidsMielinaGenesCognitionNeurodegenerative DiseasesLipidsMyelin sheathThe apolipoprotein E gene (APOE) ε4 allele has a strong and manifold impact on cognition and neuroimaging phenotypes in cognitively normal subjects, including alterations in the white matter (WM) microstructure. Such alterations have often been regarded as a reflection of potential thinning of the myelin sheath along axons, rather than pure axonal degeneration. Considering the main role of APOE in brain lipid transport, characterizing the impact of APOE on the myelin coating is therefore of crucial interest, especially in healthy APOE-ε4 homozygous individuals, who are exposed to a twelve-fold higher risk of developing Alzheimer's disease (AD), compared to the rest of the population. We examined T1w/T2w ratio maps in 515 cognitively healthy middle-aged participants from the ALFA study (ALzheimer and FAmilies) cohort, a single-site population-based study enriched for AD risk (68 APOE-ε4 homozygotes, 197 heterozygotes, and 250 non-carriers). Using tract-based spatial statistics, we assessed the impact of age and APOE genotype on this ratio taken as an indirect descriptor of myelin content. Healthy APOE-ε4 carriers display decreased T1w/T2w ratios in extensive regions in a dose-dependent manner. These differences were found to interact with age, suggesting faster changes in individuals with more ε4 alleles. These results obtained with T1w/T2w ratios, confirm the increased vulnerability of WM tracts in APOE-ε4 healthy carriers. Early alterations of myelin content could be the result of the impaired function of the ε4 isoform of the APOE protein in cholesterol transport. These findings help to clarify the possible interactions between the APOE-dependent non-pathological burden and age-related changes potentially at the source of the AD pathological cascade.Elsevier2020202020192020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/162049Articles publicats en revistes (Psicologia Clínica i Psicobiologia)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.nicl.2019.101983Neuroimage-Clinical, 2019, vol. 24, p. 101983https://doi.org/10.1016/j.nicl.2019.101983cc-by-nc-nd (c) Elsevier, 2019http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1620492026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Interactive effect of age and APOE-ε4 allele load on white matter myelin content in cognitively normal middle-aged subjects |
| title |
Interactive effect of age and APOE-ε4 allele load on white matter myelin content in cognitively normal middle-aged subjects |
| spellingShingle |
Interactive effect of age and APOE-ε4 allele load on white matter myelin content in cognitively normal middle-aged subjects Operto, Grégory Gens Cognició Malalties neurodegeneratives Lípids Mielina Genes Cognition Neurodegenerative Diseases Lipids Myelin sheath |
| title_short |
Interactive effect of age and APOE-ε4 allele load on white matter myelin content in cognitively normal middle-aged subjects |
| title_full |
Interactive effect of age and APOE-ε4 allele load on white matter myelin content in cognitively normal middle-aged subjects |
| title_fullStr |
Interactive effect of age and APOE-ε4 allele load on white matter myelin content in cognitively normal middle-aged subjects |
| title_full_unstemmed |
Interactive effect of age and APOE-ε4 allele load on white matter myelin content in cognitively normal middle-aged subjects |
| title_sort |
Interactive effect of age and APOE-ε4 allele load on white matter myelin content in cognitively normal middle-aged subjects |
| dc.creator.none.fl_str_mv |
Operto, Grégory Molinuevo, José Luis Cacciaglia, Raffaele Falcón, Carles Brugulat Serrat, Anna Suárez Calvet, Marc Grau Rivera, Oriol Bargalló Alabart, Núria Moran, Sebastian Esteller, Manel, 1968- Gispert, Juan Domingo |
| author |
Operto, Grégory |
| author_facet |
Operto, Grégory Molinuevo, José Luis Cacciaglia, Raffaele Falcón, Carles Brugulat Serrat, Anna Suárez Calvet, Marc Grau Rivera, Oriol Bargalló Alabart, Núria Moran, Sebastian Esteller, Manel, 1968- Gispert, Juan Domingo |
| author_role |
author |
| author2 |
Molinuevo, José Luis Cacciaglia, Raffaele Falcón, Carles Brugulat Serrat, Anna Suárez Calvet, Marc Grau Rivera, Oriol Bargalló Alabart, Núria Moran, Sebastian Esteller, Manel, 1968- Gispert, Juan Domingo |
| author2_role |
author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Gens Cognició Malalties neurodegeneratives Lípids Mielina Genes Cognition Neurodegenerative Diseases Lipids Myelin sheath |
| topic |
Gens Cognició Malalties neurodegeneratives Lípids Mielina Genes Cognition Neurodegenerative Diseases Lipids Myelin sheath |
| description |
The apolipoprotein E gene (APOE) ε4 allele has a strong and manifold impact on cognition and neuroimaging phenotypes in cognitively normal subjects, including alterations in the white matter (WM) microstructure. Such alterations have often been regarded as a reflection of potential thinning of the myelin sheath along axons, rather than pure axonal degeneration. Considering the main role of APOE in brain lipid transport, characterizing the impact of APOE on the myelin coating is therefore of crucial interest, especially in healthy APOE-ε4 homozygous individuals, who are exposed to a twelve-fold higher risk of developing Alzheimer's disease (AD), compared to the rest of the population. We examined T1w/T2w ratio maps in 515 cognitively healthy middle-aged participants from the ALFA study (ALzheimer and FAmilies) cohort, a single-site population-based study enriched for AD risk (68 APOE-ε4 homozygotes, 197 heterozygotes, and 250 non-carriers). Using tract-based spatial statistics, we assessed the impact of age and APOE genotype on this ratio taken as an indirect descriptor of myelin content. Healthy APOE-ε4 carriers display decreased T1w/T2w ratios in extensive regions in a dose-dependent manner. These differences were found to interact with age, suggesting faster changes in individuals with more ε4 alleles. These results obtained with T1w/T2w ratios, confirm the increased vulnerability of WM tracts in APOE-ε4 healthy carriers. Early alterations of myelin content could be the result of the impaired function of the ε4 isoform of the APOE protein in cholesterol transport. These findings help to clarify the possible interactions between the APOE-dependent non-pathological burden and age-related changes potentially at the source of the AD pathological cascade. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2020 2020 2020 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/162049 |
| url |
https://hdl.handle.net/2445/162049 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1016/j.nicl.2019.101983 Neuroimage-Clinical, 2019, vol. 24, p. 101983 https://doi.org/10.1016/j.nicl.2019.101983 |
| dc.rights.none.fl_str_mv |
cc-by-nc-nd (c) Elsevier, 2019 http://creativecommons.org/licenses/by-nc-nd/3.0/es info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by-nc-nd (c) Elsevier, 2019 http://creativecommons.org/licenses/by-nc-nd/3.0/es |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
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Elsevier |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Psicologia Clínica i Psicobiologia) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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