Biophysical alterations in lipid rafts from human cerebral cortex associate with increased BACE1/APP interaction in early stages of Alzheimer's disease

In the present study, we have assessed the biophysical properties of lipid rafts from different brain areas in subjects exhibiting early neuropathological stages of Alzheimer's disease (AD). By means of steady-state fluorescence polarization analyses using two environment-sensitive fluorescent...

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Detalles Bibliográficos
Autores: Díaz, Mario, Fabelo, Noemí, Martín, Virginia, Ferrer, Isidro (Ferrer Abizanda), Gómez, Tomás, Marín, Raquel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
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:2445/154808
Acceso en línea:https://hdl.handle.net/2445/154808
Access Level:acceso abierto
Palabra clave:Metabolisme
Malaltia d'Alzheimer
Amiloïdosi
Metabolism
Alzheimer's disease
Amyloidosis
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spelling Biophysical alterations in lipid rafts from human cerebral cortex associate with increased BACE1/APP interaction in early stages of Alzheimer's diseaseDíaz, MarioFabelo, NoemíMartín, VirginiaFerrer, Isidro (Ferrer Abizanda)Gómez, TomásMarín, RaquelMetabolismeMalaltia d'AlzheimerAmiloïdosiMetabolismAlzheimer's diseaseAmyloidosisIn the present study, we have assessed the biophysical properties of lipid rafts from different brain areas in subjects exhibiting early neuropathological stages of Alzheimer's disease (AD). By means of steady-state fluorescence polarization analyses using two environment-sensitive fluorescent probes, we demonstrate that lipid rafts from cerebellum, and frontal and entorhinal cortices, exhibit different biophysical behaviors depending on the stage of the disease. Thus, while membrane anisotropies were similar in the cerebellum along stages, lipid rafts from frontal and entorhinal cortices at AD stages I/II and AD III were significantly more liquid-ordered than in control subjects, both at the aqueous interface and hydrophobic core of the raft membrane. Thermotropic analyses demonstrated the presence of Arrhenius breakpoints between 28.3-32.0 °C, which were not influenced by the disease stage. However, analyses of membrane microviscosity (ηapp) demonstrate that frontal and entorhinal lipid rafts are notably more viscous and liquid-ordered all across the membrane from early stages of the disease. These physicochemical alterations in lipid rafts do not correlate with changes in cholesterol or sphingomyelin levels, but to reduced unsaturation index and increased saturate/polyunsaturated ratios in phospholipid acyl chains. Moreover, we demonstrate that β-secretase/AβPP (amyloid-β protein precursor) interaction and lipid raft microviscosity are strongly, and positively, correlated in AD frontal and entorhinal cortices. These observations strengthens the hypothesis that physical properties of these microdomains modulate the convergence of amyloidogenic machinery toward lipid rafts, and also points to a critical role of polyunsaturated fatty acids in amyloidogenic processing of AβPP.IOS Press2020202020152020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion14 p.application/pdfhttps://hdl.handle.net/2445/154808Articles publicats en revistes (Patologia i Terapèutica Experimental)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/10.3233/JAD-141146Journal of Alzheimer's Disease, 2015, vol. 43, num. 4, p. 1185-1198https://doi.org/10.3233/JAD-141146(c) Díaz, Mario et al., 2015info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1548082026-05-29T05:05:01Z
dc.title.none.fl_str_mv Biophysical alterations in lipid rafts from human cerebral cortex associate with increased BACE1/APP interaction in early stages of Alzheimer's disease
title Biophysical alterations in lipid rafts from human cerebral cortex associate with increased BACE1/APP interaction in early stages of Alzheimer's disease
spellingShingle Biophysical alterations in lipid rafts from human cerebral cortex associate with increased BACE1/APP interaction in early stages of Alzheimer's disease
Díaz, Mario
Metabolisme
Malaltia d'Alzheimer
Amiloïdosi
Metabolism
Alzheimer's disease
Amyloidosis
title_short Biophysical alterations in lipid rafts from human cerebral cortex associate with increased BACE1/APP interaction in early stages of Alzheimer's disease
title_full Biophysical alterations in lipid rafts from human cerebral cortex associate with increased BACE1/APP interaction in early stages of Alzheimer's disease
title_fullStr Biophysical alterations in lipid rafts from human cerebral cortex associate with increased BACE1/APP interaction in early stages of Alzheimer's disease
title_full_unstemmed Biophysical alterations in lipid rafts from human cerebral cortex associate with increased BACE1/APP interaction in early stages of Alzheimer's disease
title_sort Biophysical alterations in lipid rafts from human cerebral cortex associate with increased BACE1/APP interaction in early stages of Alzheimer's disease
dc.creator.none.fl_str_mv Díaz, Mario
Fabelo, Noemí
Martín, Virginia
Ferrer, Isidro (Ferrer Abizanda)
Gómez, Tomás
Marín, Raquel
author Díaz, Mario
author_facet Díaz, Mario
Fabelo, Noemí
Martín, Virginia
Ferrer, Isidro (Ferrer Abizanda)
Gómez, Tomás
Marín, Raquel
author_role author
author2 Fabelo, Noemí
Martín, Virginia
Ferrer, Isidro (Ferrer Abizanda)
Gómez, Tomás
Marín, Raquel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Metabolisme
Malaltia d'Alzheimer
Amiloïdosi
Metabolism
Alzheimer's disease
Amyloidosis
topic Metabolisme
Malaltia d'Alzheimer
Amiloïdosi
Metabolism
Alzheimer's disease
Amyloidosis
description In the present study, we have assessed the biophysical properties of lipid rafts from different brain areas in subjects exhibiting early neuropathological stages of Alzheimer's disease (AD). By means of steady-state fluorescence polarization analyses using two environment-sensitive fluorescent probes, we demonstrate that lipid rafts from cerebellum, and frontal and entorhinal cortices, exhibit different biophysical behaviors depending on the stage of the disease. Thus, while membrane anisotropies were similar in the cerebellum along stages, lipid rafts from frontal and entorhinal cortices at AD stages I/II and AD III were significantly more liquid-ordered than in control subjects, both at the aqueous interface and hydrophobic core of the raft membrane. Thermotropic analyses demonstrated the presence of Arrhenius breakpoints between 28.3-32.0 °C, which were not influenced by the disease stage. However, analyses of membrane microviscosity (ηapp) demonstrate that frontal and entorhinal lipid rafts are notably more viscous and liquid-ordered all across the membrane from early stages of the disease. These physicochemical alterations in lipid rafts do not correlate with changes in cholesterol or sphingomyelin levels, but to reduced unsaturation index and increased saturate/polyunsaturated ratios in phospholipid acyl chains. Moreover, we demonstrate that β-secretase/AβPP (amyloid-β protein precursor) interaction and lipid raft microviscosity are strongly, and positively, correlated in AD frontal and entorhinal cortices. These observations strengthens the hypothesis that physical properties of these microdomains modulate the convergence of amyloidogenic machinery toward lipid rafts, and also points to a critical role of polyunsaturated fatty acids in amyloidogenic processing of AβPP.
publishDate 2015
dc.date.none.fl_str_mv 2015
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/2445/154808
url https://hdl.handle.net/2445/154808
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/10.3233/JAD-141146
Journal of Alzheimer's Disease, 2015, vol. 43, num. 4, p. 1185-1198
https://doi.org/10.3233/JAD-141146
dc.rights.none.fl_str_mv (c) Díaz, Mario et al., 2015
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Díaz, Mario et al., 2015
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 14 p.
application/pdf
dc.publisher.none.fl_str_mv IOS Press
publisher.none.fl_str_mv IOS Press
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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