TY - JOUR
T1 - White Matter Hyperintensities Are No Major Confounder for Alzheimer's Disease Cerebrospinal Fluid Biomarkers
AU - Van Waalwijk Van Doorn, Linda J.C.
AU - Ghafoorian, Mohsen
AU - Van Leijsen, Esther M.C.
AU - Claassen, Jurgen A.H.R.
AU - Arighi, Andrea
AU - Bozzali, Marco
AU - Cannas, Jorge
AU - Cavedo, Enrica
AU - Eusebi, Paolo
AU - Farotti, Lucia
AU - Fenoglio, Chiara
AU - Fortea, Juan
AU - Frisoni, Giovanni B.
AU - Galimberti, Daniela
AU - Greco, Viviana
AU - Herukka, Sanna-Kaisa
AU - Liu, Yawu
AU - Lleó, Alberto
AU - De Mendonça, Alexandre
AU - Nobili, Flavio M.
AU - Parnetti, Lucilla
AU - Picco, Agnese
AU - Pikkarainen, Maria
AU - Salvadori, Nicola
AU - Scarpini, Elio
AU - Soininen, Hilkka
AU - Tarducci, Roberto
AU - Urbani, Andrea
AU - Vilaplana, Eduard
AU - Meulenbroek, Olga
AU - Platel, Bram
AU - Verbeek, Marcel M.
AU - Kuiperij, H. Bea
AU - Martins, Ralph
PY - 2021
Y1 - 2021
N2 - Background: The cerebrospinal fluid (CSF) biomarkers amyloid-β 1-42 (Aβ42), 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 Aβ42, but not p-tau and t-tau, levels with WMH volume was observed in the AD (r2 = 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 (r2 = 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 Aβ42 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.
AB - Background: The cerebrospinal fluid (CSF) biomarkers amyloid-β 1-42 (Aβ42), 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 Aβ42, but not p-tau and t-tau, levels with WMH volume was observed in the AD (r2 = 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 (r2 = 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 Aβ42 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.
KW - Alzheimer's disease
KW - amyloid
KW - biomarkers
KW - cerebrospinal fluid
KW - magnetic resonance imaging
KW - tau proteins
KW - white matter hyperintensities
KW - white matter lesions
KW - Alzheimer's disease
KW - amyloid
KW - biomarkers
KW - cerebrospinal fluid
KW - magnetic resonance imaging
KW - tau proteins
KW - white matter hyperintensities
KW - white matter lesions
UR - http://hdl.handle.net/10807/167534
U2 - 10.3233/JAD-200496
DO - 10.3233/JAD-200496
M3 - Article
SN - 1387-2877
VL - 79
SP - 163
EP - 175
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
ER -