White Matter Hyperintensities Are No Major Confounder for Alzheimer's Disease Cerebrospinal Fluid Biomarkers

Background: The cerebrospinal fluid (CSF) biomarkers amyloid-beta 1-42 (A beta(42)), total and phosphorylated tau (t-tau, p-tau) are increasingly used to assist in the clinical diagnosis of Alzheimer's disease (AD). However, CSF biomarker levels can be affected by confounding factors. Objective...

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Autores: van Doorn, LJCV, Ghafoorian, M, van Leijsen, EMC, Claassen, JAHR, Arighi, A, Bozzali, M, Cannas, J, Cavedo, E, Eusebi, P, Farotti, L, Fenoglio, C, Fortea, J, Frisoni, GB, Galimberti, D, Greco, V, Herukka, SK, Liu, YW, Lleo, A, de Mendonca, A, Nobili, FM, Parnetti, L, Picco, A, Pikkarainen, M, Salvadori, N, Scarpini, E, Soininen, H, Tarducci, R, Urbani, A, Vilaplana, E, Meulenbroek, O, Platel, B, Verbeek, MM, Kuiperij, HB
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p4178
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4178
http://ddd.uab.cat/record/238669
Access Level:acceso abierto
Palabra clave:Alzheimer's disease
amyloid
biomarkers
cerebrospinal fluid
magnetic resonance imaging
tau proteins
white matter hyperintensities
white matter lesions
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spelling White Matter Hyperintensities Are No Major Confounder for Alzheimer's Disease Cerebrospinal Fluid Biomarkersvan Doorn, LJCVGhafoorian, Mvan Leijsen, EMCClaassen, JAHRArighi, ABozzali, MCannas, JCavedo, EEusebi, PFarotti, LFenoglio, CFortea, JFrisoni, GBGalimberti, DGreco, VHerukka, SKLiu, YWLleo, Ade Mendonca, ANobili, FMParnetti, LPicco, APikkarainen, MSalvadori, NScarpini, ESoininen, HTarducci, RUrbani, AVilaplana, EMeulenbroek, OPlatel, BVerbeek, MMKuiperij, HBAlzheimer's diseaseamyloidbiomarkerscerebrospinal fluidmagnetic resonance imagingtau proteinswhite matter hyperintensitieswhite matter lesionsBackground: The cerebrospinal fluid (CSF) biomarkers amyloid-beta 1-42 (A beta(42)), total and phosphorylated tau (t-tau, p-tau) are increasingly used to assist in the clinical diagnosis of Alzheimer's disease (AD). However, CSF biomarker levels can be affected by confounding factors. Objective: To investigate the association of white matter hyperintensities (WMHs) present in the brain with AD CSF biomarker levels. Methods: We included CSF biomarker and magnetic resonance imaging (MRI) data of 172 subjects (52 controls, 72 mild cognitive impairment (MCI), and 48 AD patients) from 9 European Memory Clinics. A computer aided detection system for standardized automated segmentation of WMHs was used on MRI scans to determine WMH volumes. Association of WMH volume with AD CSF biomarkers was determined using linear regression analysis. Results: A small, negative association of CSF A beta(42), but not p-tau and t-tau, levels with WMH volume was observed in the AD (r(2) = 0.084, p = 0.046), but not the MCI and control groups, which was slightly increased when including the distance of WMHs to the ventricles in the analysis (r(2) = 0.105, p = 0.025). Three global patterns of WMH distribution, either with 1) a low, 2) a peak close to the ventricles, or 3) a high, broadly-distributed WMH volume could be observed in brains of subjects in each diagnostic group. Conclusion: Despite an association of WMH volume with CSF A beta(42) levels in AD patients, the occurrence of WMHs is not accompanied by excess release of cellular proteins in the CSF, suggesting that WMHs are no major confounder for AD CSF biomarker assessment.IOS PRESS2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4178http://ddd.uab.cat/record/238669JOURNAL OF ALZHEIMERS DISEASEISSN: 13872877ISSNe: 18758908reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p41782026-06-14T12:41:47Z
dc.title.none.fl_str_mv White Matter Hyperintensities Are No Major Confounder for Alzheimer's Disease Cerebrospinal Fluid Biomarkers
title White Matter Hyperintensities Are No Major Confounder for Alzheimer's Disease Cerebrospinal Fluid Biomarkers
spellingShingle White Matter Hyperintensities Are No Major Confounder for Alzheimer's Disease Cerebrospinal Fluid Biomarkers
van Doorn, LJCV
Alzheimer's disease
amyloid
biomarkers
cerebrospinal fluid
magnetic resonance imaging
tau proteins
white matter hyperintensities
white matter lesions
title_short White Matter Hyperintensities Are No Major Confounder for Alzheimer's Disease Cerebrospinal Fluid Biomarkers
title_full White Matter Hyperintensities Are No Major Confounder for Alzheimer's Disease Cerebrospinal Fluid Biomarkers
title_fullStr White Matter Hyperintensities Are No Major Confounder for Alzheimer's Disease Cerebrospinal Fluid Biomarkers
title_full_unstemmed White Matter Hyperintensities Are No Major Confounder for Alzheimer's Disease Cerebrospinal Fluid Biomarkers
title_sort White Matter Hyperintensities Are No Major Confounder for Alzheimer's Disease Cerebrospinal Fluid Biomarkers
dc.creator.none.fl_str_mv van Doorn, LJCV
Ghafoorian, M
van Leijsen, EMC
Claassen, JAHR
Arighi, A
Bozzali, M
Cannas, J
Cavedo, E
Eusebi, P
Farotti, L
Fenoglio, C
Fortea, J
Frisoni, GB
Galimberti, D
Greco, V
Herukka, SK
Liu, YW
Lleo, A
de Mendonca, A
Nobili, FM
Parnetti, L
Picco, A
Pikkarainen, M
Salvadori, N
Scarpini, E
Soininen, H
Tarducci, R
Urbani, A
Vilaplana, E
Meulenbroek, O
Platel, B
Verbeek, MM
Kuiperij, HB
author van Doorn, LJCV
author_facet van Doorn, LJCV
Ghafoorian, M
van Leijsen, EMC
Claassen, JAHR
Arighi, A
Bozzali, M
Cannas, J
Cavedo, E
Eusebi, P
Farotti, L
Fenoglio, C
Fortea, J
Frisoni, GB
Galimberti, D
Greco, V
Herukka, SK
Liu, YW
Lleo, A
de Mendonca, A
Nobili, FM
Parnetti, L
Picco, A
Pikkarainen, M
Salvadori, N
Scarpini, E
Soininen, H
Tarducci, R
Urbani, A
Vilaplana, E
Meulenbroek, O
Platel, B
Verbeek, MM
Kuiperij, HB
author_role author
author2 Ghafoorian, M
van Leijsen, EMC
Claassen, JAHR
Arighi, A
Bozzali, M
Cannas, J
Cavedo, E
Eusebi, P
Farotti, L
Fenoglio, C
Fortea, J
Frisoni, GB
Galimberti, D
Greco, V
Herukka, SK
Liu, YW
Lleo, A
de Mendonca, A
Nobili, FM
Parnetti, L
Picco, A
Pikkarainen, M
Salvadori, N
Scarpini, E
Soininen, H
Tarducci, R
Urbani, A
Vilaplana, E
Meulenbroek, O
Platel, B
Verbeek, MM
Kuiperij, HB
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer's disease
amyloid
biomarkers
cerebrospinal fluid
magnetic resonance imaging
tau proteins
white matter hyperintensities
white matter lesions
topic Alzheimer's disease
amyloid
biomarkers
cerebrospinal fluid
magnetic resonance imaging
tau proteins
white matter hyperintensities
white matter lesions
description Background: The cerebrospinal fluid (CSF) biomarkers amyloid-beta 1-42 (A beta(42)), total and phosphorylated tau (t-tau, p-tau) are increasingly used to assist in the clinical diagnosis of Alzheimer's disease (AD). However, CSF biomarker levels can be affected by confounding factors. Objective: To investigate the association of white matter hyperintensities (WMHs) present in the brain with AD CSF biomarker levels. Methods: We included CSF biomarker and magnetic resonance imaging (MRI) data of 172 subjects (52 controls, 72 mild cognitive impairment (MCI), and 48 AD patients) from 9 European Memory Clinics. A computer aided detection system for standardized automated segmentation of WMHs was used on MRI scans to determine WMH volumes. Association of WMH volume with AD CSF biomarkers was determined using linear regression analysis. Results: A small, negative association of CSF A beta(42), but not p-tau and t-tau, levels with WMH volume was observed in the AD (r(2) = 0.084, p = 0.046), but not the MCI and control groups, which was slightly increased when including the distance of WMHs to the ventricles in the analysis (r(2) = 0.105, p = 0.025). Three global patterns of WMH distribution, either with 1) a low, 2) a peak close to the ventricles, or 3) a high, broadly-distributed WMH volume could be observed in brains of subjects in each diagnostic group. Conclusion: Despite an association of WMH volume with CSF A beta(42) levels in AD patients, the occurrence of WMHs is not accompanied by excess release of cellular proteins in the CSF, suggesting that WMHs are no major confounder for AD CSF biomarker assessment.
publishDate 2021
dc.date.none.fl_str_mv 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://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4178
http://ddd.uab.cat/record/238669
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4178
http://ddd.uab.cat/record/238669
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv IOS PRESS
publisher.none.fl_str_mv IOS PRESS
dc.source.none.fl_str_mv JOURNAL OF ALZHEIMERS DISEASE
ISSN: 13872877
ISSNe: 18758908
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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