Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer's Disease

Alzheimer's type dementia (AD) exhibits clinical heterogeneity, as well as differences in disease progression, as a subset of patients with a clinical diagnosis of AD progresses more rapidly (rpAD) than the typical AD of slow progression (spAD). Previous findings indicate that low cerebrospinal...

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Autores: Podlesniy, Petar, Llorens Torres, Franc, Puigròs Serra, Margalida, Serra, Nuria, Sepúlveda Falla, Diego, Schmidt, Christian, Hermann, Peter, Zerr, Inga, Trullàs i Oliva, Ramon
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
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:2445/173417
Acceso en línea:https://hdl.handle.net/2445/173417
Access Level:acceso abierto
Palabra clave:ADN mitocondrial
Malaltia d'Alzheimer
Líquid cefalorraquidi
Mitochondrial DNA
Alzheimer's disease
Cerebrospinal fluid
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spelling Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer's DiseasePodlesniy, PetarLlorens Torres, FrancPuigròs Serra, MargalidaSerra, NuriaSepúlveda Falla, DiegoSchmidt, ChristianHermann, PeterZerr, IngaTrullàs i Oliva, RamonADN mitocondrialMalaltia d'AlzheimerLíquid cefalorraquidiMitochondrial DNAAlzheimer's diseaseCerebrospinal fluidAlzheimer's type dementia (AD) exhibits clinical heterogeneity, as well as differences in disease progression, as a subset of patients with a clinical diagnosis of AD progresses more rapidly (rpAD) than the typical AD of slow progression (spAD). Previous findings indicate that low cerebrospinal fluid (CSF) content of cell-free mitochondrial DNA (cf-mtDNA) precedes clinical signs of AD. We have now investigated the relationship between cf-mtDNA and other biomarkers of AD to determine whether a particular biomarker profile underlies the different rates of AD progression. We measured the content of cf-mtDNA, beta-amyloid peptide 1-42 (A beta), total tau protein (t-tau) and phosphorylated tau (p-tau) in the CSF from a cohort of 95 subjects consisting of 49 controls with a neurologic disorder without dementia, 30 patients with a clinical diagnosis of spAD and 16 patients with rpAD. We found that 37% of controls met at least one AD biomarker criteria, while 53% and 44% of subjects with spAD and rpAD, respectively, did not fulfill the two core AD biomarker criteria: high t-tau and low A beta in CSF. In the whole cohort, patients with spAD, but not with rpAD, showed a statistically significant 44% decrease of cf-mtDNA in CSF compared to control. When the cohort included only subjects selected by A beta and t-tau biomarker criteria, the spAD group showed a larger decrease of cf-mtDNA (69%), whereas in the rpAD group cf-mtDNA levels remained unaltered. In the whole cohort, the CSF levels of cf-mtDNA correlated positively with A beta and negatively with p-tau. Moreover, the ratio between cf-mtDNA and p-tau increased the sensitivity and specificity of spAD diagnosis up to 93% and 94%, respectively, in the biomarker-selected cohort. These results show that the content of cf-mtDNA in CSF correlates with the earliest pathological markers of the disease, A beta and p-tau, but not with the marker of neuronal damage t-tau. Moreover, these findings confirm that low CSF content of cf-mtDNA is a biomarker for the early detection of AD and support the hypothesis that low cf-mtDNA, together with low A beta and high p-tau, constitute a distinctive CSF biomarker profile that differentiates spAD from other neurological disorders.MDPI2021202120202021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion14 p.application/pdfhttps://hdl.handle.net/2445/173417Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))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/10.3390/ijms21176298International Journal of Molecular Sciences, 2020, vol. 21, num. 17https://doi.org/10.3390/ijms21176298cc by (c) Podlesniy et al., 2020http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1734172026-05-29T05:05:01Z
dc.title.none.fl_str_mv Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer's Disease
title Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer's Disease
spellingShingle Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer's Disease
Podlesniy, Petar
ADN mitocondrial
Malaltia d'Alzheimer
Líquid cefalorraquidi
Mitochondrial DNA
Alzheimer's disease
Cerebrospinal fluid
title_short Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer's Disease
title_full Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer's Disease
title_fullStr Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer's Disease
title_full_unstemmed Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer's Disease
title_sort Cerebrospinal Fluid Mitochondrial DNA in Rapid and Slow Progressive Forms of Alzheimer's Disease
dc.creator.none.fl_str_mv Podlesniy, Petar
Llorens Torres, Franc
Puigròs Serra, Margalida
Serra, Nuria
Sepúlveda Falla, Diego
Schmidt, Christian
Hermann, Peter
Zerr, Inga
Trullàs i Oliva, Ramon
author Podlesniy, Petar
author_facet Podlesniy, Petar
Llorens Torres, Franc
Puigròs Serra, Margalida
Serra, Nuria
Sepúlveda Falla, Diego
Schmidt, Christian
Hermann, Peter
Zerr, Inga
Trullàs i Oliva, Ramon
author_role author
author2 Llorens Torres, Franc
Puigròs Serra, Margalida
Serra, Nuria
Sepúlveda Falla, Diego
Schmidt, Christian
Hermann, Peter
Zerr, Inga
Trullàs i Oliva, Ramon
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ADN mitocondrial
Malaltia d'Alzheimer
Líquid cefalorraquidi
Mitochondrial DNA
Alzheimer's disease
Cerebrospinal fluid
topic ADN mitocondrial
Malaltia d'Alzheimer
Líquid cefalorraquidi
Mitochondrial DNA
Alzheimer's disease
Cerebrospinal fluid
description Alzheimer's type dementia (AD) exhibits clinical heterogeneity, as well as differences in disease progression, as a subset of patients with a clinical diagnosis of AD progresses more rapidly (rpAD) than the typical AD of slow progression (spAD). Previous findings indicate that low cerebrospinal fluid (CSF) content of cell-free mitochondrial DNA (cf-mtDNA) precedes clinical signs of AD. We have now investigated the relationship between cf-mtDNA and other biomarkers of AD to determine whether a particular biomarker profile underlies the different rates of AD progression. We measured the content of cf-mtDNA, beta-amyloid peptide 1-42 (A beta), total tau protein (t-tau) and phosphorylated tau (p-tau) in the CSF from a cohort of 95 subjects consisting of 49 controls with a neurologic disorder without dementia, 30 patients with a clinical diagnosis of spAD and 16 patients with rpAD. We found that 37% of controls met at least one AD biomarker criteria, while 53% and 44% of subjects with spAD and rpAD, respectively, did not fulfill the two core AD biomarker criteria: high t-tau and low A beta in CSF. In the whole cohort, patients with spAD, but not with rpAD, showed a statistically significant 44% decrease of cf-mtDNA in CSF compared to control. When the cohort included only subjects selected by A beta and t-tau biomarker criteria, the spAD group showed a larger decrease of cf-mtDNA (69%), whereas in the rpAD group cf-mtDNA levels remained unaltered. In the whole cohort, the CSF levels of cf-mtDNA correlated positively with A beta and negatively with p-tau. Moreover, the ratio between cf-mtDNA and p-tau increased the sensitivity and specificity of spAD diagnosis up to 93% and 94%, respectively, in the biomarker-selected cohort. These results show that the content of cf-mtDNA in CSF correlates with the earliest pathological markers of the disease, A beta and p-tau, but not with the marker of neuronal damage t-tau. Moreover, these findings confirm that low CSF content of cf-mtDNA is a biomarker for the early detection of AD and support the hypothesis that low cf-mtDNA, together with low A beta and high p-tau, constitute a distinctive CSF biomarker profile that differentiates spAD from other neurological disorders.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
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/2445/173417
url https://hdl.handle.net/2445/173417
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/10.3390/ijms21176298
International Journal of Molecular Sciences, 2020, vol. 21, num. 17
https://doi.org/10.3390/ijms21176298
dc.rights.none.fl_str_mv cc by (c) Podlesniy et al., 2020
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Podlesniy et al., 2020
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 14 p.
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
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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