1. White Matter Hyperintensities Are No Major Confounder for Alzheimer's Disease Cerebrospinal Fluid Biomarkers
- Author
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Van Waalwijk Van Doorn, L. J. C., Ghafoorian, M., Van Leijsen, E. M. C., Claassen, J. A. H. R., Arighi, A., Bozzali, M., Cannas, J., Cavedo, E., Eusebi, P., Farotti, L., Fenoglio, C., Fortea, J., Frisoni, G. B., Galimberti, D., Greco, V., Herukka, S. -K., Liu, Y., Lleo, A., De Mendonca, A., Nobili, F. M., Parnetti, L., Picco, A., Pikkarainen, M., Salvadori, N., Scarpini, E., Soininen, H., Tarducci, R., Urbani, A., Vilaplana, E., Meulenbroek, O., Platel, B., Verbeek, M. M., Kuiperij, H. B., and Martins, R.
- Subjects
Male ,0301 basic medicine ,Pathology ,Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1] ,tau proteins ,0302 clinical medicine ,Cerebrospinal fluid ,Leukoencephalopathies ,Image Processing, Computer-Assisted ,magnetic resonance imaging ,Phosphorylation ,medicine.diagnostic_test ,biology ,General Neuroscience ,amyloid ,Confounding Factors, Epidemiologic ,General Medicine ,Middle Aged ,Alzheimer's disease ,white matter hyperintensities ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,Psychiatry and Mental health ,Clinical Psychology ,Brain size ,Alzheimer’s disease ,biomarkers ,cerebrospinal fluid ,white matter lesions ,Female ,Research Article ,medicine.medical_specialty ,Tau protein ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,Neuroimaging ,Alzheimer Disease ,mental disorders ,medicine ,Humans ,Cognitive Dysfunction ,Memory disorder ,Settore BIO/10 - BIOCHIMICA ,Aged ,Amyloid beta-Peptides ,business.industry ,Magnetic resonance imaging ,medicine.disease ,Peptide Fragments ,Hyperintensity ,030104 developmental biology ,biology.protein ,Geriatrics and Gerontology ,business ,030217 neurology & neurosurgery - Abstract
Altres ajuts: Additionally, this work was funded by the CIBERNED program (Program 1, Alzheimer Disease), FondoEuropeo de Desarrollo Regional (FEDER), Unión Europea, "Una manera de hacer Europa" and a "Marató TV3" grant (grant number: 201412.10). The cerebrospinal fluid (CSF) biomarkers amyloid-β 1-42 (Aβ), 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. To investigate the association of white matter hyperintensities (WMHs) present in the brain with AD CSF biomarker levels. 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. A small, negative association of CSF Aβ, 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. Despite an association of WMH volume with CSF Aβ 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.
- Published
- 2021