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ABSTRACT: Background
The cerebrospinal fluid (CSF) biomarkers amyloid-? 1-42 (A?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?42, 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 A?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.
SUBMITTER: van Waalwijk van Doorn LJC
PROVIDER: S-EPMC7902951 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
van Waalwijk van Doorn Linda J C LJC Ghafoorian Mohsen M van Leijsen Esther M C EMC Claassen Jurgen A H R JAHR Arighi Andrea A Bozzali Marco M Cannas Jorge J Cavedo Enrica E Eusebi Paolo P Farotti Lucia L Fenoglio Chiara C Fortea Juan J Frisoni Giovanni B GB Galimberti Daniela D Greco Viviana V Herukka Sanna-Kaisa SK Liu Yawu Y Lleó Alberto A de Mendonça Alexandre A Nobili Flavio M FM Parnetti Lucilla L Picco Agnese A Pikkarainen Maria M Salvadori Nicola N Scarpini Elio E Soininen Hilkka H Tarducci Roberto R Urbani Andrea A Vilaplana Eduard E Meulenbroek Olga O Platel Bram B Verbeek Marcel M MM Kuiperij H Bea HB
Journal of Alzheimer's disease : JAD 20210101 1
<h4>Background</h4>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.<h4>Objective</h4>To investigate the association of white matter hyperintensities (WMHs) present in the brain with AD CSF biomarker levels.<h4>Methods</h4>We included CSF biomarker and magnetic resonance imaging (MRI) ...[more]