White Matter Hyperintensities Are No Major Confounder for Alzheimer's Disease Cerebrospinal Fluid Biomarkers
Por:
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
Publicada:
1 ene 2021
Resumen:
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.
Filiaciones:
van Doorn, LJCV:
Radboud Univ Nijmegen, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol,Med Ctr, Nijmegen, Netherlands
Radboud Univ Nijmegen, Dept Lab Med, Med Ctr, Nijmegen, Netherlands
Ghafoorian, M:
Radboud Univ Nijmegen, Dept Radiol & Nucl Med, Med Ctr, Nijmegen, Netherlands
van Leijsen, EMC:
Radboud Univ Nijmegen, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol,Med Ctr, Nijmegen, Netherlands
Claassen, JAHR:
Radboud Univ Nijmegen, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav, Dept Geriatr,Med Ctr, Nijmegen, Netherlands
Arighi, A:
Fdn IRCCS Ca Granda, Osped Policlin, Milan, Italy
Bozzali, M:
IRCCS Fdn Santa Lucia, Rome, Italy
Univ Sussex, Brighton & Sussex Med Sch, Dept Neurosci, Brighton, E Sussex, England
Cannas, J:
Univ Lisbon, Fac Med, Lisbon, Portugal
Cavedo, E:
IRCCS San Giovanni di Dio Fatebenefratelli, Lab Epidemiol Neuroimaging & Telemed, Brescia, Italy
Sorbonne Univ, Pitie Salpetriere Hosp, AP HP, Alzheimer Precis Med APM,GRC 21, Blvd Hop, Paris, France
Qynapse, Paris, France
Eusebi, P:
Univ Perugia, Ctr Memory Disturbances, Sect Neurol, Perugia, Italy
Farotti, L:
Univ Perugia, Ctr Memory Disturbances, Sect Neurol, Perugia, Italy
Fenoglio, C:
Univ Milan, Dino Ferrari Ctr, Milan, Italy
Fortea, J:
Univ Autonoma Barcelona, Dept Neurol, St Pau Memory Unit, Hosp Santa Creu & St Pau,Biomed Res Inst St Pau, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Frisoni, GB:
IRCCS San Giovanni di Dio Fatebenefratelli, Lab Epidemiol Neuroimaging & Telemed, Brescia, Italy
Univ Hosp, Geneva, Switzerland
Univ Geneva, Geneva, Switzerland
Galimberti, D:
Fdn IRCCS Ca Granda, Osped Policlin, Milan, Italy
Univ Milan, Dino Ferrari Ctr, Milan, Italy
Greco, V:
Fdn Policlin Univ A Gemelli IRCCS, Rome, Italy
Univ Cattolica, Dept Basic Biotechnol Sci, Intensivol & Perioperat Clin, Rome, Italy
Herukka, SK:
Univ Eastern Finland, Dept Neurol, Kuopio, Finland
Kuopio Univ Hosp, Kuopio, Finland
Liu, YW:
Univ Eastern Finland, Dept Neurol, Kuopio, Finland
Kuopio Univ Hosp, Kuopio, Finland
Lleo, A:
Univ Autonoma Barcelona, Dept Neurol, St Pau Memory Unit, Hosp Santa Creu & St Pau,Biomed Res Inst St Pau, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
de Mendonca, A:
Univ Lisbon, Fac Med, Lisbon, Portugal
Nobili, FM:
Univ Genoa, Dept Neurosci DINOGMI, Genoa, Italy
IRCCS Osped Policlin San Martino, Genoa, Italy
Parnetti, L:
Univ Perugia, Ctr Memory Disturbances, Sect Neurol, Perugia, Italy
Picco, A:
Univ Genoa, Dept Neurosci DINOGMI, Genoa, Italy
Pikkarainen, M:
Univ Eastern Finland, Dept Neurol, Kuopio, Finland
Kuopio Univ Hosp, Kuopio, Finland
Salvadori, N:
Univ Perugia, Ctr Memory Disturbances, Sect Neurol, Perugia, Italy
Scarpini, E:
Fdn IRCCS Ca Granda, Osped Policlin, Milan, Italy
Univ Milan, Dino Ferrari Ctr, Milan, Italy
Soininen, H:
Univ Eastern Finland, Dept Neurol, Kuopio, Finland
Kuopio Univ Hosp, Kuopio, Finland
Tarducci, R:
Univ Perugia, Ctr Memory Disturbances, Sect Neurol, Perugia, Italy
Urbani, A:
Fdn Policlin Univ A Gemelli IRCCS, Rome, Italy
Univ Cattolica, Dept Basic Biotechnol Sci, Intensivol & Perioperat Clin, Rome, Italy
Vilaplana, E:
Univ Autonoma Barcelona, Dept Neurol, St Pau Memory Unit, Hosp Santa Creu & St Pau,Biomed Res Inst St Pau, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Meulenbroek, O:
Radboud Univ Nijmegen, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav, Dept Geriatr,Med Ctr, Nijmegen, Netherlands
Platel, B:
Radboud Univ Nijmegen, Dept Radiol & Nucl Med, Med Ctr, Nijmegen, Netherlands
Verbeek, MM:
Radboud Univ Nijmegen, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol,Med Ctr, Nijmegen, Netherlands
Radboud Univ Nijmegen, Dept Lab Med, Med Ctr, Nijmegen, Netherlands
Kuiperij, HB:
Radboud Univ Nijmegen, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol,Med Ctr, Nijmegen, Netherlands
Radboud Univ Nijmegen, Dept Lab Med, Med Ctr, Nijmegen, Netherlands
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